Landscape of cohesin-mediated chromatin loops in the human genome

被引:126
作者
Grubert, Fabian [1 ,2 ]
Srivas, Rohith [1 ]
Spacek, Damek, V [1 ]
Kasowski, Maya [1 ,2 ]
Ruiz-Velasco, Mariana [3 ]
Sinnott-Armstrong, Nasa [1 ]
Greenside, Peyton [4 ]
Narasimha, Anil [1 ]
Liu, Qing [1 ]
Geller, Benjamin [1 ]
Sanghi, Akshay [1 ]
Kulik, Michael [5 ,6 ]
Sa, Silin [7 ,8 ,9 ]
Rabinovitch, Marlene [7 ,8 ,9 ]
Kundaje, Anshul [1 ,10 ]
Dalton, Stephen [5 ,6 ]
Zaugg, Judith B. [3 ]
Snyder, Michael [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Genet, Palo Alto, CA 94304 USA
[2] Stanford Univ, Sch Med, Dept Pathol, Palo Alto, CA 94304 USA
[3] European Mol Biol Lab, Struct & Computat Biol, Heidelberg, Germany
[4] Stanford Univ, Sch Med, Biomed Informat Grad Training Program, Stanford, CA 94305 USA
[5] Univ Georgia, Ctr Mol Med, Athens, GA 30602 USA
[6] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA
[7] Stanford Univ, Sch Med, Vera Moulton Wall Ctr Pulm Vasc Dis, Palo Alto, CA 94304 USA
[8] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Palo Alto, CA 94304 USA
[9] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA
[10] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
关键词
WIDE ASSOCIATION; TRANSCRIPTION FACTORS; INTEGRATIVE ANALYSIS; GENE-EXPRESSION; CONTACT MAPS; DOMAINS; ARCHITECTURE; STEM; DISRUPTION; ACTIVATION;
D O I
10.1038/s41586-020-2151-x
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
Physical interactions between distal regulatory elements have a key role in regulating gene expression, but the extent to which these interactions vary between cell types and contribute to cell-type-specific gene expression remains unclear. Here, to address these questions as part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-mediated chromatin loops, using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types, including core ENCODE cell lines. Twenty-eight per cent of all chromatin loops vary across cell types; these variations modestly correlate with changes in gene expression and are effective at grouping cell types according to their tissue of origin. The connectivity of genes corresponds to different functional classes, with housekeeping genes having few contacts, and dosage-sensitive genes being more connected to enhancer elements. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia, and will help to support emerging analyses of genome structure and function. A map of cohesin-mediated chromatin loops in 24 types of human cells identifies loops that show cell-type-specific variation, indicating that chromatin loops may help to specify cell-specific gene expression programs and functions.
引用
收藏
页码:737 / +
页数:22
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