title: Genome-wide maps of TBX1 state in transfected BCPAP cells

city: XI'AN

first: wang

address: Yanta Street

institute: Department of Endocrinology

summary: Genome wide identification of TBX1 sites of occupancy in thyroid cancer cell line BCPAP cells by comparing control BCPAP cells transfected with pcDNA3.1-Vector (cotains Myc tag) with cells transfected with pcDNA3.1-TBX1 (contains Myc tag). By obtaining over 30 Million bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of TBX1 transfected. We find that transcription factor TBX1 exerts tumor suppressive properties through regulating multiple downstream targets involved in PI3K/Akt and MAPK/Erk signaling pathways.

overall_design: Examination global levels of TBX1 in the 2 transfected cells.

first: Peng

last: Hou

last: Wang


title: Genome-wide analysis of gene expression patterns in human prostate cancer (PCa)

status: Public on Apr 22 2018

city: Berlin

first: Klaus

last: Jung

address: Schumannstr. 20/21

department: Dept. of Urology

country: Germany

institute: University Hospital Charité

summary: To investigate the mechanisms of PCa progression, we performed expression profiling of human prostate cancer and benign tissues.

overall_design: mRNA microarray expression analysis was performed by using  30 matched malignant and non-malignant prostate tissue samples from 15 PCa patients.

first: Hellmuth

last: Meyer


title: Dimethyl itaconate inhibits secondary wave of NF-κB signaling in macrophage activation

status: Public on Apr 21 2018

first: Maxim

middle: N.

last: Artyomov

state: MO

address: 660 S. Euclid Avenue, Campus Box 8118

department: Immunology&Pathology

country: USA

institute: Washington University in St.Louis

type: Expression profiling by high throughput sequencing

summary: Natural metabolite itaconate and its membrane permeable derivative dimethyl itaconate (DI) selectively inhibit a subset of cytokines during macrophage activation (e.g. IL-1β, IL-6, IL-12 but not TNF-α). Selectivity of DI action stems from the inhibitory effects of secondary, but not primary, wave of NF-κB signaling.

overall_design: Bone marrow-derived macrophages (BMDMs) from C57BL/6 mice were stimulated with LPS + IFNg for indicated timepoints. Some samples were treated with dimethyl itaconate for 12h prior to LPS stimulation.

first: Monika

last: Bambouskova

first: Vicky

last: Lampropoulou

first: Alexey

last: Sergushichev

middle: N


title: Sex differences in transcriptomic profiles in aged kidney cells of renin lineage

status: Public on Apr 30 2018

city: Box

first: Stuart

last: Shankland

state: WA

address: 1959 NE Pacific Avenue

department: Nephrology

institute: University of Washington, Seattle

summary: Renin expressing cells in the kidney’s juxta-glomeruluar compartment likely also serve as progenitors for adult glomerular cells in disease. Although these cells of renin lineage (CoRL) decrease in number with advancing kidney age, accompanied by less responsiveness to typical stimuli such as ACE-inhibition, mechanisms and the impact of sex as a biological variable with age are not known. Accordingly, labeled CoRL were sorted from individual young (2m) and aged (27m) male and female Ren1cCre|ZsGreen reporter mice, and their transcriptomic profiles analyzed by RNA seq. When both aged female and male mice were combined, there were 48 differentially expressed genes (DEG) compared to young mice. However, when compared to their young sex-matched mice, aged female and male mice had 159 and 503 DEGs respectively. In addition to marked differences in individual genes between aged female and male mice, gene ontology analysis showed major pathway differences by sex. The majority of DEGs in one sex did not significantly change or changed in the opposite direction in the other sex. These results show that in CoRL of advanced age, individual genes and gene ontologies change, but differ between female and male mice, highlighting sex related differences the aging process.

overall_design: We performed RNA-seq on 5 young (2 months) CoRL reporter mice (3 male, 2 female) and on 5 aged (27 months) inducible CoRL reporter mice (3 male, 2 female)

first: Yuliang

middle: J


title: ChIP-seq from A549 (ENCSR807WAC)

status: Public on Apr 20 2018

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

institute: ENCODE DCC

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 3 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR895JMI)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 0.5 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Genome-wide transcriptional analysis of human patterned induced neurons (hpiNs)

status: Public on Apr 24 2018

city: Cambridge

first: Ralda

last: Nehme

state: Ma

address: 415 Main St

institute: Broad Institute

summary: We report that combining NGN2 programming with SMAD and WNT inhibition generates patterned induced neurons (hpiNs).Transcriptional analyses showed that hpiN cultures contained cells along a developmental continuumranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons. The most differentiated neurons could be identified using a CAMK2A::GFP reporter gene.

overall_design: RNA sequencing analysis (population and single cell) over hpiNs differentiation time (D0 through D49 after induction). Two independent iPS lines, 9 time points, three replicates each.

first: Emanuela

last: Zuccaro


title: ChIP-seq from A549 (ENCSR956LGB)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 1 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR806UKK)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 5 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR981FDC)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 2 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR944ZCT)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 3 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR768DOX)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 1 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: RNA-seq analysis dataset: FACS-sorted Ptf1a-lineage cells from E14.5 hypothalamus of Ptf1a hetero and homozygous mice

city: Tsukuba

first: Tomoyuki

last: Fujiyama

state: Ibaraki

address: 1-1-1 Tennodai

department: International Institute for Integrative Sleep Medicine (WPI-IIIS)

country: Japan

institute: University of Tsukuba

summary: Because Ptf1a is a transcription factor, this protein should regulate transcription of various genes in Ptf1a-expressing cells of the hypothalamus. To detect those downstream genes, we purified cells in the Ptf1a-lineage from the hypothalamus at E14.5 by FACS sorting, subsequently performed RNA-seq analysis and obtained 706 differentially expressed genes. 386 genes had lower and 320 had higher expression in Ptf1a-lineage cells from homozygous Ptf1a deficient mice. The down-regulated genes included Prdm13, Corl2 and Lhx5 that were known downstream targets of Ptf1a, in addition, Sox3 and Nkx2-1, which are known to be required for hypothalamic development. Interestingly, among those affected genes, we detected several genes encoding transmembrane and/or secreted proteins, such as Jag2 (ligand for Notch receptors), Sema6b, Sema4g (ligands for Plexin family proteins). These genes may have a non-cell autonomous role in the sexual differentiation of hypothalamic cells adjacent to Ptf1a-lineage cells. Kiss1 expression was not altered, as was expected by the finding that most Kiss1-expressing cells were not in the Ptf1a lineage.

overall_design: Hypothalamic Ptf1a-lineage cell mRNA profiles of E14.5 Ptf1a-cre heterozygous and homozygous mice with Ai9 reporter were generated by FACS-sorting and RNA-sequencing, using BD Bioscience FACSAria II SORP flow cytometer and Illumina NextSeq500.

first: Masafumi

last: Muratani

first: Kazumasa

last: Kanemaru

first: Hiromasa

last: Funato


title: ChIP-seq from A549 (ENCSR853VWZ)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 6 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR760NPX)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 5 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR748MVX)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 4 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR676MJK)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 7 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR501LQA)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 6 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR537EFT)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 7 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR620NWG)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 0.5 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR335RKQ)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 4 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR247LSH)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 2 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR330ELC)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 10 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR199XBQ)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 8 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR984DZW)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 8 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIP-seq from A549 (ENCSR193NSH)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 0 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Genome wide expression data and chromatin changes data of murine cardiac fibroblasts in different topological states

city: los angeles

first: Matteo

last: Pellegrini

address: 675 Charles E Young Drive S

department: Molecular, Cell and Developmental Biology

institute: University of California, Los Angeles

summary: cardiac fibroblasts in 2D, 3D or 3D-2D or 3D-2D-3D , 2D-5days, 3D-5 days or cardiac fibroblasts grown in different stiffness of 0.5, 8 and 64 lkPA were harvested for gene expression analysis or chromatin changes analysis.

overall_design: Comparison of gene expression or chromation changes of cardiac fibroblsts in the above mentioned groups

first: Jingyi

last: Yu

first: Kai

last: Fu


title: ChIP-seq from A549 (ENCSR767DFK)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 12 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Gene expression analysis of human CD8+ T cells treated with a DOT1L inhibitor

city: Tokyo

first: Yuki

last: Kagoya

address: 35 Shinanomachi, Shinjuku

department: School of Medicine

institute: Keio University

summary: Adoptive T cell therapy (ACT) is a promising therapeutic approach for cancer patients.  The use of allogeneic T cell grafts will improve its applicability and versatility provided that inherent allogeneic responses are controlled.  Through extensive chemical probe screening, we found that inhibiting DOT1L, a histone H3-lysine 79 methyltransferase, alleviated allogeneic T cell responses.  DOT1L inhibition with SGC0946 selectively ameliorated low-avidity T cell responses but not high-avidity antitumor T cell responses mediated by the high-affinity T cell receptor or chimeric antigen receptor.  The inhibition of DOT1L in T cells prevented the development of graft-versus-host disease while retaining potent antitumor activity in xenogeneic ACT models.  These results suggest that DOT1L inhibition may enable the safe and effective use of allogeneic antitumor T cells by suppressing unwanted immunological reactions in ACT.

overall_design: To investigate how DOT1L inhibition modulates the T cell activation signal, we compared gene expression profiles between SGC0946-treated or DMSO-treated (control) T cells by RNA-sequencing analysis.  Human CD8+ T cells derived from three different healthy donors were cultured in the presence of SGC0946 or DMSO.  Total RNA was collected from each sample and gene expression profiles were analyzed by RNA-sequencing using an Illumina HiSeq 2500 sequencer.

first: Naoto

last: Hirano


title: Expression analysis of CD8+ T cells following high-avidity or low-avidity T cell receptor (TCR) stimulation in the presence or absence of a DOT1L inhibitor

summary:
Adoptive T cell therapy (ACT) is a promising therapeutic approach for cancer patients.  The use of allogeneic T cell grafts will improve its applicability and versatility provided that inherent allogeneic responses are controlled.  T cell activation is finely regulated by multiple signaling molecules that are transcriptionally controlled by epigenetic mechanisms.  Through extensive chemical probe screening, we found that inhibiting DOT1L, a histone H3-lysine 79 methyltransferase, alleviated allogeneic T cell responses.
DOT1L inhibition reduced miR-181a expression, which increased the ERK phosphatase DUSP6 expression. The inhibition of DOT1L or ectopic expression of DUSP6 in T cells prevented the development of graft-versus-host disease while retaining potent antitumor activity in multiple ACT models.  These results suggest that DOT1L inhibition may enable the safe and effective use of allogeneic antitumor T cells by suppressing unwanted immunological reactions in ACT. To further explore how DOT1L inhibition differentially affects high- and low-avidity stimulation-mediated T cell responses, gene expression profiles of DMF5- (high affinity) or cl.413- (low affinity) TCR-transduced T cells with or without SGC0946 treatment were analyzed following TCR stimulation.

overall_design: Human CD8+ T cells from three different healthy donors were transduced with HLA-A2/MART127-35-specific T cell receptor DMF5 (high affinity) or cl.413 (low affinity) and were cultured in the presence of a DOT1L inhibitor SGC0946 or control DMSO. T cells were then stimulated with artificial antigen presenting cells expressing HLA-A2 loaded with MART127-35 peptide. RNA was collected 24 hours after stimulation and gene expression profiles were analyzed by Affymetrix Human Gene 2.0 ST Array (gene-level analysis).


title: Bivalent chromatin domains in glioblastoma multiforme reveal an epigenetic signature of early neural development mediated by SHH and Wnt signaling

status: Public on Apr 19 2018

city: Austin

first: Vishy

last: Iyer

state: TX

address: 2500 Speedway Dr. MBB 3.212

department: Molecular Biosciences

institute: University of Texas at Austin

summary: We performed ChIP-seq for H3K27me3 and H3K4me3 to identify bivalent chromatin regions in T98G Glioblastoma multiforme cells.

overall_design: ChIP-seq for H3K4me3, H3K27me3 and Input in T98G cells.

first: Amelia

middle: W

last: Hall


title: Differential DNA methylation in Multiple Sclerosis

city: Shanghai

first: Yun

last: Liu

address: 130 Dong An Road

country: China

institute: Fudan University

summary:
Genome-wide DNA methylation level was studied to determine whether multiple sclerosis patients (cases) has methylation differences comparing to normal controls in PBLs.
We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in peripheral blood from multiple sclerosis patients (cases) and normal controls

overall_design: Bisulphite converted DNA from the multiple sclerosis patients (cases) and normal controls were hybridized to the Illumina Illumina HumanMethylation450 BeadChip arrays


title: DAOY-NERT2 Notch/Hypoxia Transcriptome Analysis

city: Solna

first: Urban

last: Lendahl

address: Berzelius väg 35

department: CMB

country: Sweden

institute: Karolinska Institutet

summary: Hyperactivation of Notch signaling and the cellular hypoxic response are frequently observed in cancers, with increasing reports of connections to tumor initiation and progression. The two signaling mechanisms are known to intersect, but while it is well established that hypoxia regulates Notch signaling, less is known about whether Notch can regulate the cellular hypoxic response. We now report that Notch signaling specifically controls expression of HIF2a, a key mediator of the cellular hypoxic response. Transcriptional upregulation of HIF2a by Notch under normoxic conditions leads to elevated HIF2a protein levels in primary breast cancer cells as well as in human breast cancer, medulloblastoma and renal cell carcinoma cell lines. The elevated level of HIF2a protein was in certain tumor cell types accompanied by down-regulation of HIF1a protein levels, indicating that high Notch signaling may drive a HIF1a-to-HIF2a switch. At the transcriptome level, the presence of HIF2a was required for approximately 21% of all Notch-induced genes: among the 1062 genes that were upregulated by Notch in medulloblastoma cells during normoxia, upregulation was abrogated in 227 genes when HIF2a expression was knocked down by HIF2a siRNA. In conclusion, our data show that Notch signaling affects the hypoxic response via regulation of HIF2a, which may be important for future cancer therapies.

overall_design: DAOY-NERT2 cells, +/- Notch induction by Tamoxifen (TMX) for 48 hours, +/- hypoxia (1% O2) treatment for 48 hours, where HIF1a or HIF2a had been knocked down by siRNA, were subjected to RNA sequencing. The quality of the cDNA libraries was tested on an Agilent 2100 bioanalyzer. The libraries were sequenced on an Illumina HiSeq 2000 system, and the reads were aligned to the human genome (assembly hg19) and a transcriptome database (RefSeq and Ensembl) using bowtie. RPKM values were generated using rpkmforgenes.

first: Anders

middle: P

last: Mutvei


title: ChIP-seq from A549 (ENCSR495WGO)

first: ENCODE

last: DCC

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 10 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Expression data from WT and TNFRSF19 KO HNE-1 cells

city: Guangzhou

first: Chengcheng

last: Deng

state: Guangdong

address: No.2 lujing Road

institute: Dermatology Hospital, Southern Medical University

summary:
Genetic susceptibility underlies the pathogenesis of cancer. Through genome-wide  association studies, we and others have previously identified a novel susceptibility  gene, TNFRSF19, which encodes an orphan member of the TNF receptor superfamily,  to be associated with nasopharyngeal carcinoma (NPC) and lung cancer risk. Here, we  show that TNFRSF19 is highly expressed in NPC and is required for cell proliferation  and NPC development. However, unlike most of TNF receptors, TNFRSF19 is not  involved in NF-B activation or associated with TRAF proteins. By affinity  purification, we identified TGFβ receptor type-I (TβRI) as a specific binding partner  for TNFRSF19. TNFRSF19 binds to the kinase domain of TβRI in the cytoplasm and  thereby blocks the Smad2/3 association with TβRI and subsequent signal transduction.  Ectopic expression of TNFRSF19 in normal epithelial cells confers resistance to the  cell cycle block induced by TGFβ, whereas knockout of TNFRSF19 in NPC cells  unleashes a potent TGFβ response characterized by upregulation of Smad2/3  phosphorylation and TGFβ target gene transcription. Furthermore, elevated  TNFRSF19 expression correlates with reduced TGFβ activity and poor prognosis in  NPC patients. Our data reveal that gain-of-function of TNFRSF19 in NPC represents  a mechanism by which tumor cells evade the growth-inhibitory action of TGFβ.
Hierarchical cluster assays of the differentially expressed genes between TNFRSF19 WT and KO single clones of HNE-1 cells.

overall_design: TNFRSF19 WT and KO single clones of HNE-1 cells were selected for RNA extraction and hybridization on Affymetrix microarrays.

first: Lin

last: Feng

first: Yixin

last: Zeng


title: ATAC-Seq of CD8+ T cells during activaion in vitro over the course 24 hours with and without Runx3

city: Jupiter

first: Adam

last: Getzler

state: FL

address: 130 Scripps Way

institute: TSRI-FL

summary: T cell receptor (TCR) stimulation of naïve CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naïve cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 controls de novo access to memory CTL-specific cistromes prior to the first cell division, and is essential for memory CTL differentiation. Runx3 specifically promotes accessibility of cis-acting regions highly enriched with IRF, bZIP and Prdm1-like family TF motifs, upregulates IRF4 and establishes feed-forward transcriptional circuits that induce fundamental CTL attributes in memory precursor cells. Runx3 drives uncoupling from the naïve cell state, but subsequently restrains terminal differentiation of nascent CTL by preventing high expression of the TF T-bet and slowing effector cell proliferation. Enforced Runx3 expression enhances memory CTL differentiation and increases their numbers during iterative infections. Thus, Runx3 functions in a pioneering role to initialize and then ensure memory CTL differentiate.

overall_design: 20 samples, 2 replicates each

first: H

last: Diao

first: D

last: Wang

first: M

middle: E

last: Pipkin


title: ChIP-seq from A549 (ENCSR217ELF)

summary:
RAD21 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 12 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: DNA methylation analysis of AR24Q and AR97Q SH-SY5Y cell culture samples with dihydrotestosterone

city: Nagoya

first: Naohide

last: Kondo

state: Aichi

address: 65 Tsurumai-chou, Showa-ku

department: Neurology

institute: Nagoya University

summary: Genome wide DNA methylation profiling of AR24Q and AR97Q SH-SY5Y cell culture samples. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs. Samples included 3 normal CAG repeats (AR24Q) and 3 abnormal CAG repeats (AR97Q).

overall_design: Bisulphite converted DNA from the 6 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

first: Masahisa

last: Katsuno


title: RNA-Seq of CD8+ T cells expressing different levels of Runx3 in during LCMV infection (in vivo)

first: A


title: RNA-Seq of CD8+ T cells during LCMV infection [WT infection]

overall_design: 8 samples, 3 replicates each, 2 wildtype controls

first: W

last: Rogal


title: X Chromosome Dosage Influences DNA Methylation Dynamics During Reprogramming to Mouse iPSCs

first: Rahul

last: Karnik

state: MA

address: 419 Broadway

type: Methylation profiling by high throughput sequencing

summary: A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors. Late in reprogramming, global hypomethylation is induced in a female-specific manner. Genome-wide hypomethylation in female cells affects many genomic landmarks, including enhancers and imprint control regions, and accompanies the reactivation of the inactive X-chromosome. The loss of one of the two X-chromosomes in propagating female iPSCs is associated with genome-wide methylation gain. Collectively, our findings highlight the dynamic regulation of DNA methylation at enhancers during reprogramming and reveal that X-chromosome dosage dictates global DNA methylation levels in iPSCs.

overall_design: Reduced representation bisulfite sequencing (RRBS) of male MEFs, female and male iPS cells and male reprogramming intermediates.

first: Kathrin

last: Plath

first: Alexander

last: Meissner


title: ChIP-seq from A549 (ENCSR150EFU)

summary:
SMC3 ChIP-seq on A549 cell line treated with 100 nM dexamethasone for 0 hours.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Anti-oncogenic triterpenoids from Ganoderma lucidum activate circNF1-419 to regulate lipid metabolism and promote apoptosis in glioma

status: Public on Apr 18 2018

first: Diling

last: Chen

address: No.100, Xianliezhong Road

institute: Guangdong Institute of Microbiology, Guangzhou China 510070

type: Non-coding RNA profiling by high throughput sequencing

summary: In order to confirm that L3 (G. lucidum triterpenoids fraction) could influence circRNA expression in glioma, U87 and L3-treated U87 cells were sequenced using an Illumina HiSeq 4000 sequencing system. There were 131 circRNAs identified as down-regulated and 131 circRNAs identified as up-regulated after the U87 cells were co-incubated with L3.

overall_design: Examination of circRNA sequending in 2 cell types (U87 and L3 treated U87 samples).

first: Xiaocui

last: Tang


title: Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network

city: Goyang

first: Hee-sung

last: Chae

state: Gyeonggi-do

address: Dongguk-ro 32

department: Department of pharmacy

country: South Korea

institute: Dongguk university

summary: We performed transcript profiling of sauchinone treated with various doses on HepG2 cells using the Illumina high-throughput sequencing platform and analyzed differential gene expression at the transcriptional level.

overall_design: mRNA levels were examinated in sauchinone treated with various doses, in two biological replicates.

first: Hee-Sung

first: Byoung

middle: H

last: You

first: Dong-Yeop

last: Kim

first: Hankyu

last: Lee

first: Hyuk

last: Ko

first: Hyun-Jeong

first: Young

last: Choi

first: Sun

middle: S

first: Young-Won

last: Chin


title: Expression data from progesterone receptor knockout versus heterozygous mouse ovaries

city: St Lucia

first: Lisa

last: Akison

state: QLD

address: Sir William MacGregor Building

department: Biomedical Sciences

country: Australia

institute: University of Queensland

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Epigenetic changes induced by Bacteroides fragilis toxin (BFT)

city: Baltimore

first: Winston

last: Timp

state: MD

address: 3400 N. Charles St. Clark 102A

department: Biomedical Engineering

institute: Johns Hopkins University


title: Gene expression and miRNA profiles in atrial fibrillation. Role of miR-21.

city: Pierre Bénite

first: emmanuelle

last: meugnier

address: Cens Eli Bat 2 D- Hopital Lyon Sud

country: France

summary: We used microarrays to detail the global gene expression profile in auricle tissue between controls and patients suffering from atrial fibrillation.

overall_design: auricle tissue biopsy from 4 atrial fibrillation patients and 2 control subjects were taken for RNA extraction and hybridization on Affymetrix microarrays.

first: Elodie

last: Morel

first: Philippe

last: Chevalier

first: Sophie

last: Rome

first: Emmanuelle

last: Meugnier


title: Epigenetic changes induced by Bacteroides fragilis toxin (BFT) [ATAC-seq]

summary:
Purpose: The goal of this study is to determine how BFT2 alters chromatin accessibility at relatively early time points in colon epithelial cells, and to correlate the changes in chromatin accessibility with changes in gene expression, transcription factor binding sites, and the location of common single nucleotide variants (SNVs) and differentially methylated regions (DMRs) in colorectal cancer.
Methods: HT29/C1 cells were plated at low density and allowed to grow for 4 days at 37C and 10% CO2. Afterwards, cells were either left untreated or treated with 100ng/mL BFT2 for 24 or 48 hours. After the specified time point, cells were counted and DNA was collected in order to prepare ATAC-seq libraries. ATAC-seq library was prepared as outlined by Buenrostro et al. (2013). The 4nM pooled ATAC-seq library was sequenced using the Illumina HiSeq. For each sample, three biological replicates were sequenced. After sequencing, the data was analyzed using the pipeline developed by the Kundaje lab, as outlined on ENCODE (Lee et al., 2016). Briefly, reads were trimmed, aligned and filtered using Bowtie2, and peaks were called using MACS2. The three replicate peak files were combined in order to create one consensus file for each treatment condition using an irreproducible discovery rate (IDR) threshold of 0.1. For all analyses, the “optimal set” consensus file was used.
Results: Our data show that several genes are differentially expressed after BFT treatment and these changes correlate with changes in chromatin accessibility. This correlation is mediated by an increase in chromatin accessibility at particular transcription factor binding sites. Also, sites of increased chromatin accessibility are associated with a lower frequency of common single nucleotide variants (SNVs) in CRC and with a higher frequency of common differentially methylated regions (DMRs) in CRC.
Conclusions: This study adds critical knowledge to our understanding of host-microbe interactions in the gut. While scientists have begun to analyze the effect of specific bacteria on the epigenome of colon epithelial cells, to date, no other studies have surveyed the effect of a specific bacterial toxin on chromatin accessibility in colon epithelial cells. We conclude that BFT2 alters chromatin accessibility in colon epithelial cells, and that these changes correlate with subsequent changes in gene expression. Also, sites of BFT2-induced increased chromatin accessibility are associated with a lower frequency of common single nucleotide variants (SNVs) in CRC and with a higher frequency of common differentially methylated regions (DMRs) in CRC.

overall_design: We assayed chromatin accessibility via ATAC-seq in HT29/C1 cells with and without BFT2 treatment for 24 or 48 hours, in triplicate, using Illumina HiSeq.

first: Jawara

last: Allen


title: Differentially methylated genes in saliva are linked to childhood stress

city: Madison

first: Andy

last: Madrid

state: Wisconsin

address: 600 Highland Ave

department: Neurological Surgery

institute: University of Wiconsin - Madison

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling from saliva of prepubescent girls that experiences childhood stress. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 430,000 CpGs. Data included 22 samples with LSI (stress) scores ranging from 1 (mild) to 9.5 (severe).

overall_design: Bisulphite converted DNA from the 22 samples were hybridised to the Illumina Infinium HumanMethylation450 Beadchip.

first: Ligia

middle: A

last: Papale

first: Leslie

last: Seltzer

first: Seth

middle: D

last: Pollak

first: Reid

last: Alisch


title: Spt6 association with RNAPII directs mRNA turnover during transcription

city: Chapel Hill

first: Austin

last: Hepperla

state: NC

address: 7018B Mary Ellen Jones Building

department: Genetics

institute: University of North Carolina at Chapel Hill

summary: Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription.  Spt6 interacts with elongating RNA polymerase II (RNAPII) via a tandem Src2 homology (tSH2) domain, but it is not known whether this particular interaction is required for the nucleosome reassembly activity of Spt6.  Here, we show that Spt6 recruitment to genes and its nucleosome reassembly functions are largely independent of association with RNAPII.  Instead, the Spt6-RNAPII association is required for post-transcriptional mRNA turnover.  Mechanistically, association of Spt6 with RNAPII couples the Ccr4-Not complex to the transcribed regions of genes, which we show regulates the timely deadenylation and degradation of a broad range of mRNAs including those required for cell cycle progression.  Thus, our findings reveal an unexpected control mechanism for mRNA turnover facilitated by a histone chaperone during transcription.

overall_design: RNA-seq (3 replicates) and ATAC-seq (3 replicates), along with other biochemical assays, were performed on WT vs tSH2 mutants of Spt6 to understanding the role of Spt6 in regulation of mRNA stability in yeast.

first: Raghuvar

last: Dronamraju

first: Ausin

first: Yoichiro

last: Shibata

first: Alexander

middle: T

last: Adams

first: Terry

last: Magnuson

first: Ian

last: Davis

first: Brian

last: Strahl


title: UXT is required for spermatogenesis in mice

city: New York

first: Susan

middle: K.

last: Logan

state: NY

address: 450 E 29 Street

institute: New York University School of Medicine

summary: Male mammals must simultaneously produce prodigious numbers of sperm and maintain an adequate reserve of stem cells to ensure continuous production of gametes throughout life. Failures in the mechanisms responsible for balancing germ cell differentiation and spermatogonial stem cell (SSC) self-renewal can result in infertility. We discovered a novel requirement for Ubiquitous Expressed Transcript (UXT) in spermatogenesis by developing the first knockout mouse model for this gene. Constitutive deletion of Uxt is embryonic lethal, while conditional knockout in the male germline results in a Sertoli cell-only phenotype during the first wave of spermatogenesis that does not recover in the adult. This phenotype begins to manifest between 6 and 7 days post-partum, just before meiotic entry. Gene expression analysis revealed that Uxt deletion downregulates the transcription of genes governing SSC self-renewal, differentiation, and meiosis, consistent with its previously defined role as a transcriptional co-factor. Our study has revealed the first in vivo function for UXT in the mammalian germline as a regulator of distinct transcriptional programs in SSCs and differentiating spermatogonia.

overall_design: Testes from 6 days post partum WT (Uxt F/Y) and KO (Uxt F/Y; Vasa-Cre) mice, in triplicate, were used to generate mRNA profiles using Illumina HiSeq 2500. Each pair of WT and KO samples were littermates, with replicate pairs originating from different mating cages.

first: Eric

last: Schafler

first: Phillip

last: Thomas

last: Ha

first: Yu

last: Wang

first: Keria

last: Bermudez-Hernandez

first: Zuojian

last: Tang

first: David

last: Fenyo

first: Margarita

last: Vigodner

middle: K


title: A Multi-Parameter Analysis of Cellular Coordination of Major Transcriptome Regulation Mechanisms

city: Lubbock

first: Degeng Wang

address: 1207 Gilbert Drive

department: Environmental Toxicology

institute: Texas Tech University

summary: To understand cellular coordination of multiple transcriptome regulation mechanisms, we simultaneously measured transcription rate (TR), mRNA abundance (RA) and translation activity (TA). This revealed multiple quantitative insights. First, the genomic profiles of the three parameters are systematically different in key statistical features. Sequentially more genes exhibit extreme low or high expression values from TR to RA, then to TA. That is, because of cellular coordination of these regulatory mechanisms, sequentially higher levels of gene expression selectivity are achieved as genetic information flow from the genome to the proteome. Second, the contribution of the stabilization-by-translation regulatory mechanism to the cellular coordination process was assessed. The data enabled an estimation of mRNA stability, revealing a moderate but significant positive correlation between the estimated mRNA stability and translation activity. Third, the proportion of a mRNA occupied by un-translated regions (UTR) exhibits a negative relationship with the level of this correlation, and is thus a major determinant of the mode of regulation of the mRNA. High-UTR-proportion mRNAs tend to defy the stabilization-by-translation regulatory mechanism, staying out of the polysome but remaining stable; mRNAs with little UTRs largely follow this regulation. In summary, we quantitatively delineated the relationship among multiple transcriptome regulation parameters, i.e., cellular coordination of corresponding regulatory mechanisms.

overall_design: Simultaneous measurement of transcription rate with GRO-seq, mRNA abundance with RNA-seq and mRNA translation activity with polysome profiling

first: Degeng


title: Adipocyte long noncoding RNA transcriptome analysis of obese mice identified Lnc-leptin which regulates Leptin

city: Singapore

first: Jia

last: Li

address: 8 College Road

country: Singapore

institute: Duke-NUS

summary: Obesity induces profound transcriptome changes in adipocytes; recent evidence suggests that lncRNAs play key roles in this process. Here, we performed a comprehensive transcriptome study by RNA-Seq in adipocytes isolated from interscapular brown, inguinal and epididymal white adipose tissues in diet-induced obese mice. Our analysis reveals a set of obesity-dysregulated lncRNAs, many of which exhibit dynamic changes in fed vs. fasted state, potentially serving as novel molecular markers reflecting adipose energy status. Among the most prominent ones is Lnc-leptin, an lncRNA transcribed from an enhancer region upstream of Leptin. Expression of Lnc-leptin is sensitive to insulin and closely correlates to Leptin expression across diverse pathophysiological conditions. Functionally, induction of Lnc-leptin is essential for adipogenesis, and its presence is required for a loop formation between exon2 of Lnc-leptin and promoter of Leptin in mature adipocytes and the maintenance of Leptin expression in vitro and in vivo. Our study establishes Lnc-leptin as a new regulator of Leptin.

overall_design: For inguinal and epididymal adipocytes, RNA-Seq experiments on biological triplicates were performed per diet per type of adipocyte. For interscapular brown adipocytes, only one biological sample was collected per diet. In order to collect a substantial floating adipocyte layer, each biological sample consists of tissues from 3-5 mice.

first: Kinyui

last: Lo

first: Lei

last: Sun


title: Profiling of differential RNAs in LY500307-treated 4T1 cells and control cells

status: Public on Apr 25 2018

city: Chengdu

first: Shengtao

last: Zhou

address: #17, Renmin South Road

department: Department of Obstetrics and Gynecology

institute: West China Second Hospital, Sichuan University

summary: In this study, we examined the differential RNA profile of LY500307-treated 4T1 cells compared with control-treated 4T1 cells

overall_design: We used RNA sequencing to compare the differential RNAs of LY500307-treated 4T1 cells compared with control-treated 4T1 cells


title: Runx3 pioneers chromatin accessibility of cis-regulatory landscapes that drive memory CTL formation

first: Adam

last: Getzler

summary:
T cell receptor (TCR) stimulation of naïve CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naïve cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 controls de novo access to memory CTL-specific cistromes prior to the first cell division, and is essential for memory CTL differentiation. Runx3 specifically promotes accessibility of cis-acting regions highly enriched with IRF, bZIP and Prdm1-like family TF motifs, upregulates IRF4 and establishes feed-forward transcriptional circuits that induce fundamental CTL attributes in memory precursor cells. Runx3 drives uncoupling from the naïve cell state, but subsequently restrains terminal differentiation of nascent CTL by preventing high expression of the TF T-bet and slowing effector cell proliferation. Enforced Runx3 expression enhances memory CTL differentiation and increases their numbers during iterative infections. Thus, Runx3 functions in a pioneering role to initialize and then ensure memory CTL differentiate.
This SuperSeries is composed of the SubSeries listed below.

first: A

first: H

last: Diao

first: D

first: M

last: Pipkin


city: Amsterdam

first: Liqin

address: Plesmanlaan 121

country: Netherlands

institute: NKI-AVL

type: Genome variation profiling by high throughput sequencing

summary:
BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance, which is frequently caused by reactivation of the Mitogen Activated Protein Kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor (HDACi) vorinostat represses SLC7A11 that leads to a lethal increase in the already elevated levels of ROS in drug-resistant cells, thereby causing selective apoptotic death of only the drug resistant tumor cells. Consistently, treatment of BRAF inhibitor-resistant melanoma with HDACi in mice results in a dramatic tumor regression. In a study in patients with advanced BRAF+MEK inhibitor resistant melanoma, we find that HDACi can selectively ablate drug-resistant tumor cells, providing clinical proof of concept for the novel therapy identified here.
DNA Seq data: biopy samples from patients pre- and post- treated with Vorinostat; check mutations related to MAPKi-resistance

overall_design: one replicate of DNA _178 gene panel , paired end,  patient samples pre-post vorinostat treated

first: Marja

last: Nieuwland

first: Roel

last: Kluin


title: TRAPSeq identifies transcripts enriched/de-enriched in mouse GnRH neurons.

city: Ann Arbor

first: Richard

middle: C

last: McEachin

state: United States

address: 2800 Plymouth Road

department: DCM&B

institute: University of Michigan

summary:
We utilized translating ribosome affinity purification (TRAP) coupled with RNA sequencing to examine mRNAs of GnRH neurons in adult intact and gonadectomized (GDX) male and female mice.
TRAP produces one RNA fraction enhanced for GnRH neuron transcripts and one RNA fraction depleted. cDNA libraries were created from each fraction and 50-base, paired-end sequencing done and differential expression
(enhanced fraction/depleted fraction) determined with a threshold of >1.5 or <0.66 fold (false discovery rate p≤0.05). A core of ~840 genes were differentially expressed in GnRH neurons in all treatments, including enrichment for Gnrh1 (~40 fold),
and genes critical for GnRH neuron and/or gonadotrope development. In contrast, non-neuronal transcripts were not enriched or were de-enriched. Several epithelial markers were also enriched,
consistent with the olfactory epithelial origins of GnRH neurons. Interestingly, many synaptic transmission pathways were de-enriched, in accordance with relatively low innervation of GnRH neurons.
The most striking difference between intact and GDX mice of both sexes was a marked down regulation of genes associated with oxidative phosphorylation and upregulation of glucose transporters in GnRH neurons from GDX mice.

overall_design: Exmaination of transcripts enriched in GnRH neurons in female, male, and gonadectomized mice (of both sexes) by TRAPSeq.

first: Laura

last: Burger


title: RNA Seq data: A375, A375R, A375DR vorinostat treated, and biopy samples from patients pre- and post- treated with Vorinostat

summary: BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance, which is frequently caused by reactivation of the Mitogen Activated Protein Kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor (HDACi) vorinostat represses SLC7A11 that leads to a lethal increase in the already elevated levels of ROS in drug-resistant cells, thereby causing selective apoptotic death of only the drug resistant tumor cells. Consistently, treatment of BRAF inhibitor-resistant melanoma with HDACi in mice results in a dramatic tumor regression. In a study in patients with advanced BRAF+MEK inhibitor resistant melanoma, we find that HDACi can selectively ablate drug-resistant tumor cells, providing clinical proof of concept for the novel therapy identified here.

overall_design: one replicate of RNA Seq data A375, A375R, A375DR vorinostat treated and patient samples pre- post- vorinostat treatment

first: Iris

last: de Rink


title: Chromatin Associated RNA-Seq of CD8+ T cells expressing different levels of Runx3 in a cell culture model of CTL differentiation [Chr Assoc]

summary: T cell receptor (TCR) stimulation of naïve CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naïve cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 controls de novo access to memory CTL-specific cistromes prior to the first cell division, and is essential for memory CTL differentiation. Runx3 specifically promotes accessibility of cis-acting regions highly enriched with IRF, bZIP and Prdm1-like family TF motifs, upregulates IRF4 and establishes feed-forward transcriptional circuits that induce fundamental CTL attributes in memory precursor cells. Runx3 drives uncoupling from the naïve cell state, but subsequently restrains terminal differentiation of nascent CTL by preventing high expression of the TF T-bet and slowing effector cell proliferation. Enforced Runx3 expression enhances memory CTL differentiation and increases their numbers during iterative infections. Thus, Runx3 functions in a pioneering role to initialize and then ensure memory CTL differentiate.

overall_design: 6 samples, 2 replicates each, 2 wildtype controls

last: Wang


title: Altered gene-regulatory function of KDM5C by a novel mutation associated with autism and intellectual disability

first: Christina

last: Vallianatos

state: MI

address: 1241 East Catherine

department: Human Genetics

summary: We describe a new variant in histone demethylase KDM5C in a male with autism and intellectual disability

overall_design: We performed RNA-Seq from primary mouse forebrain neuronal culture. Libraries were depleted for rRNA and strand-specific according to the protocol described in PMID: 25607527

first: Shigeki

last: Iwase


title: Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9

status: Public on Apr 17 2018

city: La Jolla

first: Gene

last: Yeo

address: 9500 Gilman Dr

department: Cellular and Molecular Medicine

institute: University of California, San Diego

summary: Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of voltage-gated calcium channel CaV1.3 are subject to brain-selective A-to-I RNA editing by ADAR2.  Here, we show that editing of CaV1.3 mRNA is dependent on a 40 bp RNA duplex formed between exon 41 and an evolutionarily conserved editing site complementary sequence (ECS) located within the preceding intron.  Heterologous expression of a mouse minigene that contained the ECS, intermediate intronic sequence and exon 41 with ADAR2 yielded robust editing. Interestingly, editing of CaV1.3 was potently inhibited by serine/arginine-rich splicing factor 9 (SRSF9). Mechanistically, the inhibitory effect of SRSF9 required direct RNA interaction. Selective down-regulation of SRSF9 in neurons provides a basis for the neuron-specific editing of CaV1.3 transcripts.

overall_design: eCLIP-seq for HA-SRSF9 in HEK293 cells

first: Hua

last: Huang

first: Katannya

last: Kapeli

first: Wenhao

last: Jin

first: Yuk

last: Wong

first: Thiruma

middle: V

last: Arumugam

first: Joanne

last: Koh

first: Sumitra

last: Srimasorn

first: Karthik

last: Mallilankaraman

first: Jia

last: Chua

first: Tuck

last: Soong


title: Gli1-expressing cells form the essential niche for colon stem cells and serve as a reserve Wnt-source in the small intestine

city: Zurich

first: Tomas

last: Valenta

address: Winterthurerstrasse 190

department: Institute of Molecular Life Sciences

country: Switzerland

institute: University of Zurich

summary: Purpose: to determine cellular heterogeneity of mesenchymal Gli1-positive cells from colon using single cell RNAse (10xGenomics); Summary: We determined 8 disctinct sub-populations of mesenchymal cells, remaining non-Gli1 epithelial cells formed a distinct separete cluster serving as a internal control of the single cells sequencing procedure

overall_design: Gli1-tdTomato cells were sorted using FACS (tdTomato positvity), single cell RNA sequencing was perfomed (for details see Degirmenci et al, in prep)

first: Konrad

last: Basler


title: Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity

city: Houston,

first: Hari Krishna

last: Yalamanchili

address: 1250 Moursund St #1125,

institute: Baylor College of Medicine

summary: Clinical trials are currently underway to assess the efficacy of forniceal deep brain stimulation (DBS) for the improvement of memory in Alzheimer’s patients, and forniceal DBS has been shown to improve learning and memory in a mouse model of Rett syndrome (RTT), an intellectual disability disorder. The mechanism of DBS benefits has been elusive, however, so we assessed gene expression, splice isoform abundance, DNA methylation, and proteomic changes following acute forniceal DBS in wild-type mice and a mouse model lacking Mecp2, the gene whose loss of function causes RTT. We found that DBS upregulates genes involved in synaptic function, cell survival, and neurogenesis, and alters the proportions of different isoforms even for genes whose expression is unchanged. DBS rescued ~25% of the gene expression defects in Mecp2-null mice, particularly those involved in synaptic components, and it induced expression of 17-24% of the genes found to be downregulated in intellectual disability mouse models and in post-mortem human brain tissue from patients with Major Depressive Disorder. DBS could thus benefit individuals with a variety of neuropsychiatric disorders.

overall_design: mRNA-Sequencing was performed on dentate gyrus tissue from wild type (WT) and MeCP2-heterozygous (Het) females. There are two treatment groups: sham treated (unstimulated) and deep brain stimulation (DBS) treated. Each sample is a biological replicate. There are 7 Het samples: 3 sham treated, 4 DBS treated. There are 8 WT samples: 4 sham treated and 4 DBS treated.

first: Amy

last: Pohodich

first: Hari

first: Zhandong

last: Liu

first: Huda

last: Zoghbi


title: Epigenetic changes induced by Bacteroides fragilis toxin (BFT) [RNA-seq]

first: Winston

last: Timp

summary:
Purpose: The goal of this study is to determine how BFT2 alters chromatin accessibility at relatively early time points in colon epithelial cells, and to correlate the changes in chromatin accessibility with changes in gene expression, transcription factor binding sites, and the location of common single nucleotide variants (SNVs) and differentially methylated regions (DMRs) in colorectal cancer.
Methods: HT29/C1 cells were plated at low density and allowed to grow for 4 days at 37C and 10% CO2. Afterwards, cells were either left untreated or treated with 100ng/mL BFT2 for 24 or 48 hours. After the specified time point, cells were counted and RNA was collected in order to prepare RNA-seq libraries. RNA was collected using the Qiagen RNeasy mini kit. mRNA was enriched using the NEBNext Poly(A) mRNA Magnetic Isolation Module. Afterwards, a non-directional RNA-seq library was constructed using the NEBnext Ultra RNA Library Prep kit from Illumina. The 2nM pooled RNA-seq library was sequenced using the Illumina HiSeq.
Results: After sequencing, Kallisto was used to perform pseudoalignment of the raw RNA-seq data. Then, Sleuth was used to quantify gene expression and perform differential expression analyses. After treatment with BFT2 for 24 hours, 70 genes were differentially expressed (P-value < 0.01). Of these genes, 41 showed a decrease in gene expression, while 29 showed an increase in gene expression. After BFT2 treatment for 48 hours, we found only 16 differentially expressed genes (P-value < 0.01); 3 showed a decrease in gene expression and 13 showed an increase in gene expression.
Conclusions: This study adds critical knowledge to our understanding of host-microbe interactions in the gut. While scientists have begun to analyze the effect of specific bacteria on the epigenome of colon epithelial cells, to date, no other studies have surveyed the effect of a specific bacterial toxin on chromatin accessibility in colon epithelial cells. We conclude that BFT2 alters chromatin accessibility in colon epithelial cells, and that these changes correlate with subsequent changes in gene expression. Also, sites of BFT2-induced increased chromatin accessibility are associated with a lower frequency of common single nucleotide variants (SNVs) in CRC and with a higher frequency of common differentially methylated regions (DMRs) in CRC.

overall_design: Gene expression in HT29/C1 cells with and without BFT2 treatment for 24 or 48 hours was assessed, in triplicate, using Illumina HiSeq.

first: Jawara

last: Allen


title: Srf destabilizes cell identity (ChIP-seq)

city: Kyoto

first: Takashi

last: Ikeda

address: 53 Shogoin Kawahara-cho Sakyo-ku

institute: Kyoto Univ.

summary: Multicellular organisms consist of multiple cell types, whose identities are maintained appropriately at locations where they are reside. The identity of each cell type is primarily maintained by cell-type-specific gene expression programs, but mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease β-actin monomer resulted in nuclear accumulation of Mkl1 and the activation of Srf, which downregulated cell-type-specific genes and altered epigenetics in enhancers and chromatin organization. Mice overexpressing Srf exhibited various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.

overall_design: Genomic binding regions of DNA-binding proteins

first: Takafusa

last: Hikichi

first: Akira

last: Watanabe

first: Takuya

last: Yamamoto

first: Keisuke

last: Okita

first: Shinji

last: Masui


title: Identification of the tumour transition states occurring during EMT

city: Bruxelles

first: Cedric

last: Blanpain

address: 808, route de Lennik, CP 637

country: Belgium

institute: Université Libre de Bruxelles (ULB)

summary: scRNAseq of YFP+ Epcam+ and Epcam- skin squamous cell carcinoma cells

overall_design: Examination of transcriptional differences in Epcam- and Epcam+ cells

first: Ievgenia

last: Pastushenko

first: Audrey

last: Brisebarre

first: Alejandro

last: Sifrim

first: Thierry

last: Voet


title: BRD4 profiling identifies critical Chronic Lymphocytic Leukemia oncogenic circuits and reveals sensitivity to PLX51107, a novel structurally distinct BET inhibitor

city: Columbus

first: Hatice Gulcin

last: Ozer

state: OH

address: 1800 Cannon Dr

department: Biomedical Informatics

institute: The Ohio State University

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Elevated mTOR signaling increases the expression of lysosome genes, but does not alter the expression of inflammatory profiles of microglia as evaluated by low input RNAseq analysis.

city: Albany

first: Yunfei

last: Huang

state: New York

address: 47 New Scotland Ave

department: Neuroscience and Experimental Therapeutics

institute: Albany Medical College

summary: The RNA-seq data was generated to evaluate the efforts of elevated mTOR signaling on the inflammatory transcriptome in the mouse microglia.  Our data shows that there were no significant differences in expression levels of major proinflammatory cytokines, chemokines and inflammatory mediators.  However, there was a significant induction of lysosome genes, along with up- or down-regulation of genes involved in phagocytosis in TSC1 knockout microglia.

overall_design: Mouse brains were harvested from four pairs of wildtype and TSC1Cx3cr1CKO mice at 4 weeks of age.  Microglia were freshly isolated utilizing anti-Cx3cr1-PE antibody (Biolegend), coupled with anti-PE MicroBeads (Miltenyi).  Microglia were finally captured using magnetic MS column (Miltenyi).  Approximately 96.8 % of purified cells were CD11b positive.  Total RNA samples were immediately prepared from purified cells using Trizol method.

first: Xiaofeng

last: Zhao

first: Xinjun

last: Zhu


title: Isolated Iliac Cryptococcosis in an Immunocompetent Patient

city: Fuzhou

first: junjun

last: sang

address: No.168 Xierhuanbei Road

institute: Fuzhou General Hospital

summary: Cryptococcal osteomyelitis is an infrequent infection which is usually associated with disseminated cryptococcosis or underlying immunocompromised conditions. Here we described a rare case with isolated iliac cryptococcosis in an immunocompetent patient. Through histological, microbial, and molecular biological examinations, the pathogen was finally identified as C. neoformans VNI genotype, which likely originated from environmental bird droppings. The clinical isolate was hypomelanized but fully virulent in mouse infection model. The patient displayed lower CD4+-T lymphocyte ratio, reduced serum IFN-γ and IL-12, and dysregulated transcriptional profile of blood leukocytes compare with healthy host. After surgical excision and 34 weeks’ antifungal treatment, the patient got clinical cured. Our study suggested that cryptococcosis development was closely associated with the interaction of fungal agent and host immunity. Accurate diagnosis of bone cryptococcosis depends mainly on histological and fungal examinations. A combination of antifungal agent treatment regimen and surgery were quite effective for resolving bone cryptococcosis.

overall_design: mRNA profiles of an Immunocompetent Patient and  normal control's blood were generated by deep sequencing, using Illumina HiSeq 2500

first: Junjun

last: Sang

first: Wei

last: Fang


title: BRD4 profiling identifies critical Chronic Lymphocytic Leukemia oncogenic circuits and reveals sensitivity to PLX51107, a novel structurally distinct BET inhibitor [ChIP-seq]

summary: Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is over-expressed in CLL and is enriched proximal to genes up-regulated or de novo expressed in CLL with known function in disease pathogenesis and progression. These genes, including key members of the BCR signaling pathway, provide rationale for this therapeutic approach to identify new targets in alternative types of cancer.  Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in pre-clinical models of CLL.  Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.

overall_design: ChIP-sequencing profiles of BRD4, H3K27Ac and RNA Pol 2, and ATAC-seq profiles for four patient cell lines under basal, stimulated and treated conditions.

first: Rosa

last: Lapalombella

first: John

last: Byrd

first: Hatice

middle: G


title: Comparative DNA methylation profiling of ICF patients supports a functional link between ZBTB24, CDCA7 and HELLS at genomic regions with heterochromatin features

city: EVRY

first: Nizar

last: Touleimat

address: 2 rue Gaston Crémieux

department: Centre National de Génotypage

institute: Commissariat à l'Energie Atomique

summary: Genome wide DNA methylation profiling of normal and ICF blood samples. The Illumina Infinium Human Methylation 450 BeadChip was used to obtain DNA methylation profiles across approximately 485,000 CpGs in whole blood from healthy and ICF subjects. Samples included 10 healthy subjects, 8 ICF1, 4 ICF2, 2 ICF3 and 1 ICF4 patients.

overall_design: Bisulphite converted DNA from the 25 samples were hybridised to the The Illumina Infinium Human Methylation 450 BeadChip

first: Giacomo

last: Grillo

first: Claire

last: Francastel


title: Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS

city: Princeton

first: Kristina

middle: Marie

last: Garske

email: kmgarske@ucla.edu, kg8086@princeton.edu

state: New Jersey

address: Carl Icahn Lab, South Drive, Princeton University

department: Lewis-Sigler Institute for Integrative Genomics; Ecology & Evolutionary Biology

institute: Princeton University

summary:
We perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression.

David Pan was funded through
Grant Title: Biomedical Big Data Training Grant
Grant ID: T32LM012424
Funding Source:  National Institutes of Health-National Cancer Institute

Marcus Alvarez was funded through
Grant Title: NIH training grant in Genomic Analysis and Interpretation
Grant ID: T32HG002536
Funding Source:  National Institutes of Health

overall_design: Promoter Capture Hi-C library was produced from human white adipocytes differentiated from primary human white preadipocytes

first: David

middle: Z

last: Pan

middle: M

first: Päivi

last: Pajukanta

first: Arthur

last: Ko


title: An acquired vulnerability of drug resistant melanoma with therapeutic potential

first: Liqin

last: Wang


title: Transcriptomes of Tgfbr2 Knockout Microglia and Macrophages

status: Public on Apr 16 2018

city: Stockholm

first: Ewoud

last: Ewing

address: CMM L8:05, Karolinska University Hospital

department: Clinical Neuroscience

institute: Karolinska Institutet

summary: The cytokine transforming growth factor-B (TGF-B) regulates development and homeostasis of several tissue-resident macrophage populations, including microglia. TGF-B is not critical for microglia survival, but is required for the maintenance of the microglia-specific homeostatic gene signature. Under defined host conditions circulating monocytes can compete for the microglial niche and give rise to long-lived monocyte-derived macrophages residing in the central nervous system (CNS). Whether monocytes require TGF-B for colonization of the microglial niche and maintenance of CNS integrity is unknown. We found that abrogation of TGF-B signaling in CX3CR1+ monocyte-derived macrophages led to rapid onset of a progressive and fatal demyelinating motor disease characterized by myelin-laden giant macrophages throughout the spinal cord. The devastating motor disease that developed in TGF-BR2-deficient chimeras indicated that in the absence of TGF-B signaling the CNS environment licenses monocyte-derived macrophages for tissue damage. We therefore addressed how the gene expression signature of CNS macrophages was controlled by TGF-B signaling. We thus sorted TGF-BR2-deficient monocyte-derived macrophages from animals with ongoing motor disease and from their wildtype littermate counterparts. For comparison we sorted wild-type and TGF-BR2-deficient microglia and performed RNA sequencing for all four groups. Tgfbr2-deficient macrophages were characterized by high expression of genes encoding proteins involved in antigen presentation, inflammation and phagocytosis. TGF-B is thus crucial for the functional integration of monocytes into the CNS microenvironment.

overall_design: Transcriptome sequencing of WT and conditional-Tgfbr2 knockout microglia and CNS-repopulating monocyte-derived macrophages from C57BL/6 mouse in triplicates

first: Harald

last: Lund


title: Variable extent of lineage-specificity and developmental stage-specificity of cohesin and CTCF binding within the immunoglobulin and T cell receptor loci

first: Salvatore

last: Loguercio

state: California

address: 10550 North Torrey Pines Rd

department: MB

institute: TSRI

summary: The large antigen receptor (AgR) loci in T and B lymphocytes have many bound CTCF sites, most of which are only occupied in lymphocytes, while only the CTCF sites at the far end of each locus near enhancers or J genes tend to be bound in non-lymphoid cells also. However, despite the generalized lymphocyte restriction of CTCF binding in AgR loci, the Igκ locus is the only locus which also shows significant lineage-specificity (T vs. B cells) and developmental stage-specificity (pre-B, not pro-B) in CTCF binding. Cohesin is often bound at the same sites as CTCF, and cohesin is thought to create long range chromatin contacts by loop extrusion, with its translocation stopped by convergently oriented CTCF sites. Importantly, cohesin binding shows greater lineage- and stage- specificity than CTCF at most loci, thus providing more specificity to the CTCF/cohesin loops in AgR loci. Since all the CTCF sites within the large V portions of the Igh and TCRβ loci have the same orientation, this suggests either a lack of requirement for convergent CTCF sites creating loops, or indicates an absence of any loops between CTCF sites within the V region portion of those loci but only loops to the convergent sites at the D‐J‐enhancer end of each locus. The V region portions of the Igκ and TCRα δ loci, in contrast, have CTCF sites in both orientations, providing many options for creating CTCF-mediated loops throughout the loci. The immune system may have developed unique utilization of CTCF sites to generate lymphocyte-specific long-range loops to facilitate the formation of diverse antigen receptor repertoires.

overall_design: For the ChIP-seq, input and immunoprecipitated DNA was given to the Next Generation Sequencing Core, where it was prepared for massively parallel sequencing on Illumina HiSeq2000.

first: Edgar

last: Barajas-Mora

first: Han-Yu

last: Shih

first: Michael

last: Krangel

first: Ann

middle: J

last: Feeney


title: LH3 overexpression reverses profound alterations of gene transcriptional profile in cerebral vessels in hypertension-induced spontaneous intracerebral hemorrhage

city: beijing

first: li

last: Michael

address: beiqing road

institute: Basepedia

summary: To gain mechanistic insights into the protection effects of lysyl hydroxylase (LH3) on reducing the susceptibility to intracerebral hemorrhage(ICH), a whole transcriptomic analysis of cerebral vessels were performed using RNA-seq. It is noteworthy that our preliminary data demonstrated that mice did not developed ICH until day 7 after AngII plus L-NAME infusion, cerebral vessels for RNA-seq were acquired at day 5 in order to provide the mechanistic or causal evidence of a direct participatory role of LH3 to the protection effects of ICH.

overall_design: 15 samples. There are 3 groups: GFP-Veh group, mice were stereotactic injection of AAV-GFP and treated with saline. GFP-AL group, mice were stereotactic injection of AAV-GFP and treated with AngII plus L-NAME. LH3-AL group, mice were stereotactic injection of AAV-LH3 and treated with AngII plus L-NAME. Mice of each group were transcardially perfused with ice-cold phosphate-buffered saline, brain were collected and cerebral vessels were isolated.

first: Hao

last: Li

first: Hao-chen

last: Xu


title: A Nucleosome Destabilizing Factor that Facilitates Transcription in Chromatin

city: Piscataway

first: Jia

last: Fei

address: 604 Allison Road

department: Molecular Biology and Biochemistry

institute: Rutgers University - New Brunswick

summary: Our understanding of transcription by RNA polymerase II (Pol II) is limited by our knowledge of the factors that mediate this critically important process. Here we describe the identification of NDF, a nucleosome destabilizing factor that facilitates Pol II transcription in chromatin. NDF has a PWWP motif, interacts with nucleosomes near the dyad, destabilizes nucleosomes in an ATP-independent manner, and facilitates transcription by Pol II through nucleosomes in a purified and defined transcription system as well as in cell nuclei. Upon transcriptional induction, NDF is recruited to the transcribed regions of thousands of genes and co-localizes with a subset of H3K36me3-enriched regions. Notably, the recruitment of NDF to gene bodies is accompanied by an increase in the transcript levels of many of the NDF-enriched genes. In addition, the global loss of NDF results in a decrease in the RNA levels of many genes. In humans, NDF is present at high levels in all tested tissue types, is essential in stem cells, and is frequently overexpressed in breast cancer. These findings indicate that NDF is a nucleosome destabilizing factor that is recruited to gene bodies during transcriptional activation and facilitates Pol II transcription through nucleosomes.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
ChIP-seq analysis of NDF and H3K36me3 in HeLa S3 (WT) and NDF CRISPR-knockout (KO) cells; ChIP-seq of NDF and H3K36me3 in mouse primary bone marrow-derived macrophages (BMDM) treated with Kdo2-Lipid A (KLA) for 0 h or 6 h; RNA-seq of HeLa WT and KO cells; RNA-seq of mouse BMDMs treated with KLA for 0h or 6 h; GRO-seq analysis of WT and NDF KO cells.

Please note that the 'diffNDF7regions_F8_6hKLA_vs_notx.*' files (available on Series records) are generated from both BMDM_ChIP_NDF7_0hKLA and BMDM_ChIP_NDF7_6hKLA samples.

first: Haruhiko

last: Ishii

first: Marten

last: Hoeksema

first: Christopher

last: Glass

first: Bing

last: Ren

first: James

last: Kadonaga


title: Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle

city: St Lucia

first: Frédéric

last: Gachon

address: 306 Carmody Road

department: Institute for Molecular Bioscience

institute: University Of Queensland

summary: The circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin stimulated glucose uptake were significantly reduced upon CLOCK depletion. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans.

overall_design: 10 candidates with 6 biopsies each for a total of 57 samples being sequenced. Together with GSE109825, part of the same study described above.

first: Laurent

last: Perrin

first: Ursula

last: Loizides-Mangold

first: Stéphanie

last: Chanon

first: Cédric

last: Gobet

first: Nicolas

last: Hulo

first: Laura

last: Isenegger

first: Benjamin

last: Weger

first: Eugenia

last: Migliavacca

first: Aline

last: Charpagne

last: Betts

first: jean-Philippe

last: Walhin

first: Iain

last: Templeman

first: Keith

last: Stokes

first: Dylan

last: Thompson

first: Kostas

last: Tsintzas

first: Maud

last: Robert

last: Howald

first: Howard

last: Riezman

first: Jerome

middle: N

last: Feige

first: Leonidas

last: Karagounis

first: Jonathan

last: Johnston

first: Emmanouil

last: Dermitzakis

first: Etienne

last: Lefai

first: Charna

last: Dibner


title: Transcriptome analysis of the developing Drosophila ovary

city: Rochester

first: Benoit

middle: of

last: Biteau

state: NEW YORK

address: 601 Elmwood Avenue, Box 633

department: Biomedical Genetics

institute: University of Rochester Medical Center

summary: Here we report the transcriptional profile of the developing Drosophila ovaries and transcriptional changes caused by dLmx1a mutation

overall_design: This study is a comparison of RNAseq from larval Fatbody and Fatbody+Ovaries in dLmx1a heterygous and homozyogous females

first: Andrew

middle: W

last: Allbee


title: Critical role for Lymphocytes in Producing FLT3LG in Tumors and Driving Checkpoint Therapy-Receptive Immune Microenvironments

status: Public on Apr 14 2018

city: San Francisco

first: Saurabh

last: Asthana

state: CA

address: 1450 Third Street, Room HD276

department: Helen Diller Family Comprehensive Cancer Center

institute: UCSF

summary: Intratumoral stimulatory dendritic cells (SDCs) play an important role in locally restimulating cytotoxic T cells and driving immune responses against cancer. However, the mechanisms that control SDC numbers remain poorly understood. In human melanoma, SDC numbers correlated with intratumoral expression of the gene encoding the cytokine FLT3LG, and we subsequently found in mouse and human tumors that this cytokine was predominantly produced by lymphocytes, notably including natural killer (NK) cells. NK cells stably formed conjugates with SDCs in the mouse tumor microenvironment (TME) and genetic and cellular ablation of NK cells in mice demonstrated their importance in regulation of SDC numbers through production of Flt3L. Although anti-PD-1 “checkpoint” immunotherapy for cancer largely targets T cells, we found that NK cells correlated with protective SDCs in human cancers, with patient responsiveness to anti-PD-1 immunotherapy, and with better overall survival. Our studies reveal that innate immune SDCs and NK cells cluster together as the best prognostic tool for T cell directed immunotherapy and that these innate cells are necessary for enhanced T cell tumor responses, suggesting this axis for novel therapies.

overall_design: This dataset is n=11 biologically independent metastatic melanoma samples from patient tumors. There is no control dataset.

first: Kevin

last: Barry

first: Joy

last: Hsu

first: Miranda

middle: L

last: Broz

first: Francisco

last: Cueto

first: Mikhail

last: Binnewies

first: Alexis

last: Combes

first: Amanda

middle: E

last: Nelson

first: Kimberly

last: Loo

first: Raj

last: Kumar

first: Michael

last: Rosenblum

last: Alvarado

first: Denise

last: Wolf

first: Dusan

last: Bogunovic

first: Nina

last: Bhardwaj

first: Adil

middle: I

last: Daud

first: Patrick

last: Ha

first: William

middle: R

last: Ryan

first: Joshua

last: Pollack

first: Bushra

last: Samad

first: Vincent

last: Chan

first: Matthew

middle: F

last: Krummel


title: RNA deep sequencing from murine BALB/c WT and IL-2-KO bulk CD8 T cells

status: Public on Apr 15 2018

city: Merced

first: Katrina

last: Hoyer

address: 5200 North Lake Road

institute: University of California, Merced

summary: Our goal was to identify early genetic changes in the development of autoimmune dysfunction. WT and IL-2-KO CD8 T cells were sorted from the lymph node and spleen of 12-day old mice. Total RNA was isolated by Expression Analysis Inc. using Illumina TrueSeq Stranded Total RNA Sample Preparation Kit. Eight samples were sequenced (four biological replicates of IL-2-KO and WT/HET mice), producing 2X50 paired-end reads using the Illumine HiSeq 2500 platform. Raw reads were provided by Expression Analysis. We identified several genetic signatures within the bulk data including a cytolyic pattern and a novel gene expression pattern indicating a helper-like function.

overall_design: WT and IL-2-KO CD8 T cells were sorted from the lymph node and spleen of 12-day old mice. Total RNA was isolated by Expression Analysis Inc. using Illumina TrueSeq Stranded Total RNA Sample Preparation Kit. Eight samples were sequenced (four biological replicates of IL-2-KO and WT/HET mice).

first: Suzanne

middle: S

last: Sindi

first: Travis

last: Lawrence

first: Kristen

last: Valentine


title: Uterine glands synchronize embryo-endometrial interactions and coordinate on-time embryo implantation and stromal cell decidualization for pregnancy success

status: Public on Apr 13 2018

city: Columbia

first: Thomas

last: Spencer

state: MO

address: 920 East Campus Drive

department: Animal Sciences

institute: University of Missouri

summary: By employing FOXA2-deficient mouse models coupled with LIF repletion, we reveal definitive roles of uterine glands in pregnancy establishment.These studies provide original evidence that uterine glands synchronize embryo-endometrial interactions, coordinate on-time embryo implantation, and impact stromal cell decidualization, thereby ensuring embryo viability, placental growth, and pregnancy success.

overall_design: Uterine transcriptomes of control and Foxa2-deficient mice were generated on gestational day (GD) 4 and GD 6 following LIF-repletion. All time points were done in quadruplicates.

first: Andrew

last: Kelleher

first: Jessica

last: Milano-Foster

first: Susanta

middle: K

last: Behura


title: Exacerbated S. aureus foot infections in obese/diabetic mice are associated with impaired germinal center reactions, Ig class-switching, and humoral immunity.

city: St. Louis

first: Christopher

last: Farnsworth

state: Missouri

address: 425 So Euclid Ave

department: Pathology

institute: Washington University in St. Louis

summary: Seq. of popliteal l/n of obese and lean mice 3 months after HF feeding

overall_design: Mice were fed a HF diet (opensource diets) for 3 mo to induce obesity/T2D prior to harvest of PLN for analysis.

first: Robert

middle: A

last: Mooney


title: Seletive inhibition of CDK9 in DLBCL cell lines

city: Portland

first: Alexey

last: Danilov

state: OR

address: 3181 SW Sam Jackson Pk Rd

institute: Oregon Health and Science Univeristy

summary: Deregulation of the MYC transcription factor is a key driver in lymphomagenesis. MYC induces global changes in gene expression that contribute to cell growth, proliferation and oncogenesis by stimulating the activity of RNA polymerases. A key feature in its ability to stimulate RNA Pol II activity is recruitment of pTEFb, an elongation factor whose catalytic core comprises CDK9/cyclin T complexes. Hence, MYC expression and function may be susceptible to CDK9 inhibition. Non-specific inhibitors of multiple CDKs have shown promise in B-cell malignancies, where their pro-apoptotic effect has been attributed to a reduction in transcription and downmodulation of short lived pro-survival proteins (e.g., Mcl-1). However, they lack a defined mechanism of action. Here we selectively targeted CDK9 in a pre-clinical study in DLBCL.

overall_design: We employed gene expression profiling by RNA-Seq to determine which pathways were deregulated by AZ5576, a selective CDK9 inhibitor, in DLBCL cells. VAL cells and OCI-LY3 cells were treated with 0.3 µM AZ-5576 for 3 or 6 hours and comparisons in gene expression were made to vehicle-treated cells. Expression of 30,451 genes was detected in DLBCL cells. Using a cutoff of at least 2-fold change we identified between one and three thousand genes whose expression was significantly affected by AZ5576

first: Taylor

last: Hashiguchi

middle: V


title: Transcriptome profiling of Cryptosporidium parvum infected lung and intestinal organoids

status: Public on Apr 12 2018

city: Utrecht

first: Devanjali

last: Dutta

state: Netherlands

address: Uppsalalaan 8

institute: Hubrecht Institute

summary:
Purpose: Transcriptome profiling of Crytosporidium parvum infected lung and small intestinal organoids was performed to access the response of epithelial cells upon parasitic infection and to do a temporal analysis of the transcriptome of the parasite inside the organoid lumen.
We isolated RNA from infected human lung and small intestinal organoids at 24 and 72 hour post infection.
Methods: Organoids were grown in expansion or differentiation media and microinjected with equal amounts of Cryptosporidium oocysts. Media-injected organoids were used as a control .Expanding SI organoids were microinjected at 5-6 days after seeding, differentiated SI organoids were injected at 5 days after inducing differentiation. Lung organoids were incubated for 2 weeks after seeding for microinjection. RNA was extracted from 1-2 matrigel drops containing organoids. RNA was converted to cDNA and libraries were prepared using the CelSeq2 method and sequenced. Samples were sequenced on Illumina NextSeq500 by using 75-bp paired-end sequencing.
Methods:    Paired-end reads from Illumina sequencing were aligned to the human transcriptome genome and C. parvum transcriptome genome (Iowa strain) by BWA. DeSeq (v1.18.0) was used for read normalization and differential expression analysis (p-value adjustment 0.05 by method Benjamini-Hochberg). Gene set enrichment analysis (GSEA) was performed using gene lists for type I interferon response and regulation against normalized RNA-seq reads of injected SI and lung organoids using GSEA software v3.0 beta2.
Results: At 24 hr post-infection,GO (gene ontology)-term analysis revealed that a substantial number of genes related to ‘cytoskeleton’ and ‘cell mobility’ were up-regulated in lung organoids. This suggests that infection by the parasites and subsequent formation of the intracellular stages within 24 hrs might affects cytoskeleton structures of host cells. After 72 hrs, many genes associated with the type I interferon pathway increased dramatically in lung and intestinal organoids.
Results: After 72 hrs, many genes associated with the type I interferon pathway increased dramatically in lung and intestinal organoids. Multiple C. parvum genes were differentially expressed with a large fold change between 24 and 72 hr post-injection.At 24 hr post-infection, most of the enriched genes represented ribosomal proteins and ribosomal RNA subunits in both intestinal organoids and lung organoids. By contrast, at 72 hr post-infection, multiple oocyst-wall protein genes were up-regulated, confirming that the parasites formed new oocysts within the organoids.
Conclusions: RNA sequencing of injected organoids revealed host epithelial responses upon parasite infection in differentiated SI organoids as well as in lung organoids.Upregulation of genes associated with type I interferon immunity in both SI and lung organoids.

overall_design: mRNA profiles of C. parvum infected human lung and intestinal organoids were generated by Deep Sequencing. Transcriptome profiles were generated from 2 human donors and samples were prepared in triplicates (Illumina NextSeq500 by using 75-bp paired-end sequencing).

first: Hans

last: Clevers

first: Roberta

last: O'Conner

first: Inha

last: Heo


title: Fasting-induced JMJD3 histone demethylase epigenetically activates mitochondrial fattyacid beta-oxidation

city: Urbana

first: Jongsook

middle: Kim

last: Kemper

state: Illinois

address: 524 Burrill Hall  407 S. Goodwin Ave

department: Department of Molecular & Integrative Physiology

institute: University of Illinois at Champaign-Urbana

summary: Jumonji D3 (JMJD3) histone demethylase epigenetically regulates development, differentiation, and immunity by demethylating a gene-repression histone mark, H3K27-me3, but a role for JMJD3 in metabolic regulation has not been described. SIRT1 deacetylase maintains energy balance during fasting by directly activating both hepatic gluconeogenic and mitochondrial fatty acid  beta-oxidation genes, but the underlying epigenetic and gene-specific mechanisms remain unclear. To explore global hepatic functions of JMJD3, mRNA levels in control and JMJD3-downregulated hepatocytes were compared by RNA-seq analysis. Expression of 2,772 and 2,143 genes was significantly decreased and increased, respectively, over 1.5-fold, by downregulation of JMJD3.  ). In gene ontology analysis, genes downregulated with the highest significance were those involved in mitochondrial functions, particularly oxidation/reduction, the respiratory chain, and fatty acid beta-oxidation, Overall, in this study, JMJD3 was shown unexpectedly to be a gene-specific transcriptional partner of SIRT1 and these epigenetic factors interact with the  nuclear receptor PPARalpha to epigenetically activate mitochondrial  beta-oxidation, but not gluconeogenic, genes during fasting.

overall_design: Liver mRNA profiles were generated by deep sequencing, were profiled in primary mouse hepatocytes in which JMJD3 was downregulated by infection with lentivirus expressing JMJD3 shRNA or by infection with control lentivirus.

first: Sunmi

last: Seok

first: Young-Chae

last: Kim

first: Sangwon

last: Byun

first: Sunge

last: Choi

first: Zhen

last: Xiao

first: Naoki

last: Iwamori

first: Yang

last: Zhang

first: Chaochen

last: Wang

first: Jina

last: Ma

first: Kai

last: Ge

first: Byron


title: Gene expression changes induced by the BET inhibitor GSK525762 and/or the MEK inhibitor trametinib in cancer cell lines.

city: Collegeville

first: Satyajit

last: Rajapurkar

state: PA

address: 1250S. Collegeville Rd.

institute: GlaxoSmithKline LLC

summary: Transcriptional changes were analyzed in two colorectal cancer, two pancreatic cancer, and one small cell lung cancer cell line following treatment with the BET inhibitor GSK525762 and/or the MEK inhibitor trametinib using Affymetrix Human Genome U133 Plus 2.0 Arrays.

overall_design: The RKO colon cancer cell line was treated with DMSO (control), 500nM GSK525762, 30nM trametinib, or a combination of two agents for 24 or 96 hours.  The colon cancer cell line COLO 201 and the pancreatic cancer cell lines HPAF-II and BxPC-3 were treated with DMSO, 500nM GSK525762, trametinib (3nM for COLO 201; 10 nM for HPAF-II and BxPC-3), or a combination of two agents for 96 hours.  The small cell lung cancer cell line NCI-H510 was treated with 1000nM GSK525762 for 24 or 96 hours. Two biological replicates are included for each treatment group.

first: Anastasia

last: Wyce

first: Daniel

last: Felitsky

first: Michael

middle: T

last: McCabe

first: Olena

last: Barbash


title: Widespread intronic polyadenylation diversifies immune cell transcriptomes

status: Public on May 04 2018

city: Bryan

first: Irtisha

last: Singh

state: TX

address: 8447 Riverside Pkwy Medical Research and Education Building II

institute: Texas A&M Health Science Center

summary: Alternative cleavage and polyadenylation (ApA) can generate mRNA isoforms with differences in 3'UTR length without changing the coding region (CDR). However, ApA can also recognize intronic polyadenylation (IpA) signals to generate transcripts that lose part or all of the CDR. We analyzed 46 3'-seq and RNA-seq profiles from normal human tissues, primary immune cells, and multiple myeloma (MM) samples and created an atlas of 4,927 high confidence IpA events represented in these cell types. Up to 16% of expressed genes in immune cells generate IpA isoforms, a majority of which are differentially used during B cell development or in different cellular environments, while MM cells display a striking loss of IpA isoforms expressed in plasma cells (PCs), their cell type of origin. IpA events can lead to truncated proteins lacking C-terminal functional domains. This can mimic ectodomain shedding through loss of transmembrane domains or alter the binding specificity of proteins with DNA-binding or protein-protein interaction domains, thus contributing to diversification of the transcriptome.  In MM, loss of expression of PC IpA isoforms is associated with shorter progression-free survival and impacts key genes in MM biology and response to the therapeutic lenalidomide, including those encoding the transcription factor IKZF1 and core E3 ubiquitin ligase complex component CUL4A.

overall_design:
Examination of IpA isoforms in primary immune cells and patients with multiple myeloma (MM). The study is primarily focused on 3'-seq samples:
29 samples from current study
17 samples from SRP029953
There are also 18 RNA-seq experiments which were used for verification of IpA events focusing in the introns of the genes.

first: Shih-Han

last: Lee

first: Christina

last: Leslie

first: Christine

last: Mayr


title: Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces cerevisiae genome

city: Athens

first: Wentao

last: Li

state: GA

address: 500 D. W Brooks Drive

department: Environmental Health Science

institute: University of Georgia

summary: We have adapted the eXcision Repair-sequencing (XR-seq) method to generate single-nucleotide resolution dynamic repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts [(6-4)PPs] in the Saccharomyces cerevisiae genome. We find that these photoproducts are removed from the genome primarily by incisions 13-18 nucleotides 5’ and 6-7 nucleotides 3’ to the UV damage that generate 21-27 nt-long excision products. Analyses of the excision repair kinetics both in single genes and at the genome-wide level reveal strong transcription-coupled repair of the transcribed strand (TS) at early time points followed by predominantly non-transcribed strand (NTS) repair at later stages. We have also characterized the excision repair level as a function of transcription level. The availability of high-resolution and dynamic repair maps should aid in future repair and mutagenesis studies in this model organism.

overall_design: We performed XR-seq for UV-induced CPD and (6-4)PP repair in wild type yeast cells. Our analysis intergreted the published datasets from RNA-seq and NET-seq (GEO accession: GSE68484) and CPD-seq (GEO accession: GSE79977).

first: Ogun

last: Adebal

first: Yanyan

last: Yang

first: Christopher

middle: P

last: Selby

first: Aziz

last: Sancar


title: Temporal RNA-seq analysis of human skeletal myotubes synchronized in vitro

city: Geneva

first: Cedric

last: Howald

state: Geneva

address: Campus Biotech, Chemin des Mines 9

institute: Health2030 Genome Center

overall_design: 100 samples from 2 donors. Together with GSE108539, part of the same study described above.

first: Laurent

last: Perrin

first: Ursula

last: Loizides-Mangold

first: Stéphanie

last: Chanon

first: Cédric

last: Gobet

first: Nicolas

last: Hulo

first: Laura

last: Isenegger

first: Benjamin

middle: D

last: Weger

first: Eugenia

last: Migliavacca

first: Aline

last: Charpagne

first: James

last: Betts

first: jean-Philippe

last: Walhin

first: Iain

last: Templeman

first: Keith

last: Stokes

first: Dylan

last: Thompson

first: Kostas

last: Tsintzas

first: Maud

last: Robert

first: Howard

last: Riezman

first: Jerome

last: Feige

first: Leonidas

middle: G

last: Karagounis

first: Jonathan

last: Johnston

first: Emmanouil

last: Dermitzakis

first: Frédéric

last: Gachon

first: Etienne

last: Lefai

first: Charna

last: Dibner


title: Identification of differentially expressed miRNAs between SW480 and SW620 spheroid cultures

city: Belvaux

first: Elisabeth

last: Letellier

address: 6, Avenue du Swing

department: Life Sciences Research Unit

country: Luxembourg

institute: University of Luxembourg

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: This SuperSeries is composed of the SubSeries listed below.

platform_organism:
Homo sapiens
synthetic construct

overall_design: Refer to individual Series


title: Identification of differentially expressed genes between SW480 and SW620 spheroid cultures [mRNA]

summary:
The colorectal cancer (CRC) cell line pair SW480/SW620 is an accepted model to study CRC progression and metastasis formation. Studying gene expression differences might allow to uncover molecular mechanisms that underlie metastasis initiation
Both cell lines are derived from the same patient, but at different stages of the disease. They might show differences in tumor-initiating cell (TIC) potential.

overall_design: Spheroid cultures of both cell lines were used to specifically look for differences in the TIC compartment of both cell lines. Three technical replicates were used for both conditions.


title: Expression analysis of Escherichia coli CC72 before and after osmotic stress

status: Public on Apr 11 2018

city: Tianjin

first: Zhe

last: Sun

address: 32 West 7th Ave

institute: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences

summary:
Expression level of whole genome genes in Escherichia coli CC72 at early-exponential phase, and 10 min, 20 min and 45 min after osmotic stress.
Venus was fused to the 3' end of rpoC in E. coli MG1655 to localize RNA polymerase as reported previously (C. Cagliero and D. J. Jin, 2013).

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: 8 chips were used to measure total RNA extracted from E. coli CC72 grown in LB medium at eary-exponential phase, and 10 min, 20 min and 45 min after 5 M NaCl stress. Each condition has two biological replicates.  And each chip measures the expression level of 4252 genes from E. coli MG 1655 eight 60 mers probe pairs (PM/MM) per gene, with two technical replicates.

first: Ding

middle: J

last: Jin