Control of Cell Identity Genes Occurs in Insulated Neighborhoods in Mammalian Chromosomes

被引:665
作者
Dowen, Jill M. [1 ]
Fan, Zi Peng [1 ,2 ]
Hnisz, Denes [1 ]
Ren, Gang [3 ,4 ]
Abraham, Brian J. [1 ]
Zhang, Lyndon N. [1 ,5 ]
Weintraub, Abraham S. [1 ,5 ]
Schuijers, Jurian [1 ]
Lee, Tong Ihn [1 ]
Zhao, Keji [3 ]
Young, Richard A. [1 ,5 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA
[3] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA
[4] Northwest A&F Univ, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China
[5] MIT, Dept Biol, Cambridge, MA 02139 USA
基金
美国国家卫生研究院; 奥地利科学基金会;
关键词
TRANSCRIPTIONAL REGULATION; DEVELOPMENTAL REGULATORS; TOPOLOGICAL DOMAINS; GENOME ORGANIZATION; SUPER-ENHANCERS; BINDING SITES; PROTEIN CTCF; CHROMATIN; COHESIN; POLYCOMB;
D O I
10.1016/j.cell.2014.09.030
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here, we use ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.
引用
收藏
页码:374 / 387
页数:14
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