title: LncPRESS1 Is a p53-Regulated LncRNA that Safeguards Pluripotency by Disrupting SIRT6-Mediated De-acetylation of Histone H3K56.
abstract: Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome-wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors. RNA-seq of hESCs depleted of lncPRESS1 revealed that lncPRESS1 controls a gene network that promotes pluripotency. Further, we found that lncPRESS1 physically interacts with SIRT6 and prevents SIRT6 chromatin localization, which maintains high levels of histone H3K56 and H3K9 acetylation at promoters of pluripotency genes. In summary, we describe a p53-regulated, pluripotency-specific lncRNA that safeguards the hESC state by disrupting SIRT6 activity.
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Stem Cell and Development Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: ajain@mdanderson.org.
authors.forename: Abhinav K
authors.initials: AK
authors.lastname: Jain
authors.affiliation: Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Stem Cell and Development Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: McCarthy
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Stem Cell and Development Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Kendra
authors.initials: K
authors.lastname: Allton
authors.affiliation: Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Kadir C
authors.initials: KC
authors.lastname: Akdemir
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
authors.forename: Lalit R
authors.initials: LR
authors.lastname: Patel
authors.affiliation: Division of Biomedical Informatics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Aronow
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chunru
authors.initials: C
authors.lastname: Lin
authors.affiliation: Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Stem Cell and Development Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: mbarton@mdanderson.org.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Barton
mesh_terms: D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D006655:Histone Deacetylases; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; C516592:SIRT6 protein, human; D037761:Sirtuins; D006655:Histone Deacetylases
keywords: H3K56ac; H3K9ac; SIRT6; chromatin; differentiation; genome-wide; hESC; lncRNA; p53; pluripotency