ChIP-Seq identification of weakly conserved heart enhancers

被引：336

作者：

Blow, Matthew J. ^{[1
,2
]}

McCulley, David J. ^{[3
,4
]}

Li, Zirong ^{[5
]}

Zhang, Tao ^{[2
]}

Akiyama, Jennifer A. ^{[1
]}

Holt, Amy ^{[1
]}

Plajzer-Frick, Ingrid ^{[1
]}

Shoukry, Malak ^{[1
]}

Wright, Crystal ^{[2
]}

Chen, Feng ^{[2
]}

Afzal, Veena ^{[1
]}

Bristow, James ^{[2
]}

Ren, Bing ^{[5
]}

Black, Brian L. ^{[3
,4
]}

Rubin, Edward M. ^{[1
,2
]}

Visel, Axel ^{[1
,2
]}

Pennacchio, Len A. ^{[1
,2
]}

机构：

[1] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA

[2] Energy Joint Genome Inst, US Dept, Walnut Creek, CA USA

[3] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

[5] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 09期

关键词：

REGULATORY ELEMENTS; GENOME; DATABASE; MECHANISMS; VERTEBRATE; CONSTRAINT; PROMOTERS; EVOLUTION; SEQUENCES; 1-PERCENT;

D O I：

10.1038/ng.650

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme noncoding-sequence conservation has successfully predicted enhancers that are active in many tissues but has failed to identify substantial numbers of heart-specific enhancers. Here, we used ChIP-Seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over 3,000 candidate heart enhancers genome wide. Compared to enhancers active in other tissues we studied at this time point, most candidate heart enhancers were less deeply conserved in vertebrate evolution. Nevertheless, transgenic mouse assays of 130 candidate regions revealed that most function reproducibly as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary conservation of embryonic enhancers can vary depending on tissue type.

引用

页码：806 / U107

页数：7

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