Large-scale discovery of enhancers from human heart tissue

被引：209

作者：

May, Dalit ^{[1
]}

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

Kaplan, Tommy ^{[3
,4
]}

McCulley, David J. ^{[5
]}

Jensen, Brian C. ^{[6
]}

Akiyama, Jennifer A. ^{[1
]}

Holt, Amy ^{[1
]}

Plajzer-Frick, Ingrid ^{[1
]}

Shoukry, Malak ^{[1
]}

Wright, Crystal ^{[2
]}

Afzal, Veena ^{[1
]}

Simpson, Paul C. ^{[5
,7
]}

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

Black, Brian L. ^{[5
]}

Bristow, James ^{[1
,2
]}

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

Visel, Axel ^{[1
,2
]}

机构：

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

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

[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA

[4] Hebrew Univ Jerusalem, Sch Comp Sci & Engn, Jerusalem, Israel

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

[6] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA

[7] Virginia Med Ctr, Div Cardiol, San Francisco, CA USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 01期

关键词：

CORONARY-ARTERY-DISEASE; GENOME BROWSER DATABASE; TRANSCRIPTIONAL NETWORK; P300; ASSOCIATION; EXPRESSION; UPDATE; IDENTIFICATION; COACTIVATORS; ELEMENTS;

D O I：

10.1038/ng.1006

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified similar to 6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.

引用

页码：89 / U125

页数：7

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