title: Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network.
abstract: BRD7 is a single bromodomain-containing protein that functions as a subunit of the SWI/SNF chromatin-remodeling complex to regulate transcription. It also interacts with the well-known tumor suppressor protein p53 to trans-activate genes involved in cell cycle arrest. In this paper, we report an integrative analysis of genome-wide chromatin occupancy of BRD7 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and digital gene expression (DGE) profiling by RNA-sequencing upon the overexpression of BRD7 in human cells. We localized 156 BRD7-binding peaks representing 184 genes by ChIP-sequencing, and most of these peaks were co-localized with histone modification sites. Four novel motifs were significantly represented in these BRD7-enriched regions. Ingenuity pathway analysis revealed that 22 of these BRD7 target genes were involved in a network regulating cell death and survival. DGE profiling identified 560 up-regulated genes and 1088 down-regulated genes regulated by BRD7. Using Gene Ontology and pathway analysis, we found significant enrichment of the cell cycle and apoptosis pathway genes. For the integrative analysis of the ChIP-seq and DEG data, we constructed a regulating network of BRD7 downstream genes, and this network suggests multiple feedback regulations of the pathways. Furthermore, we validated BIRC2, BIRC3, TXN2, and NOTCH1 genes as direct, functional BRD7 targets, which were involved in the cell cycle and apoptosis pathways. These results provide a genome-wide view of chromatin occupancy and the gene regulation network of the BRD7 signaling pathway.
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Heran
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000502:physiology; D058645:Denaturing Gradient Gel Electrophoresis; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins
keywords: Apoptosis; BRD7; Cell cycle; ChIP-sequencing; Digital gene expression (DGE)