Dissecting super-enhancer hierarchy based on chromatin interactions

被引：177

作者：

Huang, Jialiang ^{[1
,2
,3
,4
]}

Li, Kailong ^{[5
]}

Cai, Wenqing ^{[3
,4
]}

Liu, Xin ^{[5
]}

Zhang, Yuannyu ^{[5
]}

Orkin, Stuart H. ^{[3
,4
,6
]}

Xu, Jian ^{[5
]}

Yuan, Guo-Cheng ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA

[2] Harvard TH Chan Sch Publ Hlth, Boston, MA 02215 USA

[3] Harvard Med Sch, Dana Farber Canc Inst, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02215 USA

[4] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Childrens Med Ctr, Res Inst, Dallas, TX 75390 USA

[6] Howard Hughes Med Inst, Boston, MA 02215 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

HI-C DATA; CELL IDENTITY GENES; HUMAN GENOME; REGULATORY ELEMENTS; SATURATING MUTAGENESIS; TRANSCRIPTION FACTORS; ARCHITECTURE; DISEASE; DNA; ACTIVATION;

D O I：

10.1038/s41467-018-03279-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants. Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape. As such, hub enhancers are the major constituents responsible for SE functional and structural organization.

引用

页数：12

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