Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network

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• 作者：Ke Xu ; Wei Xiong ; Ming Zhou ; Heran Wang ; Jing Yang…
• 关键词：BRD7 ; ChIP ; sequencing ; Digital gene expression (DGE) ; Apoptosis ; Cell cycle
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：411
• 期：1-2
• 页码：57-71
• 全文大小：5,658 KB
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• 作者单位：Ke Xu (1) (2)
  Wei Xiong (1) (2) (3)
  Ming Zhou (1) (2) (3)
  Heran Wang (1) (2)
  Jing Yang (2)
  Xiayu Li (3)
  Pan Chen (1)
  Qianjin Liao (1)
  Hao Deng (3)
  Xiaoling Li (1) (2) (3)
  Guiyuan Li (1) (2) (3)
  Zhaoyang Zeng (1) (2) (3)
  
  1. Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
  2. 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
  3. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919

文摘

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. Keywords BRD7 ChIP-sequencing Digital gene expression (DGE) Apoptosis Cell cycle