Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation

被引：243

作者：

Raisner, Ryan ^{[1
]}

Kharbanda, Samir ^{[2
]}

Jin, Lingyan ^{[1
]}

Jeng, Edwin ^{[3
,4
]}

Chan, Emily ^{[5
]}

Merchant, Mark ^{[5
]}

Haverty, Peter M. ^{[6
]}

Bainer, Russell ^{[6
]}

Cheung, Tommy ^{[7
]}

Arnott, David ^{[7
]}

Flynn, E. Megan ^{[8
]}

Romero, F. Anthony ^{[9
]}

Magnuson, Steven ^{[10
]}

Gascoigne, Karen E. ^{[1
]}

机构：

[1] Genentech Inc, Dept Discovery Oncol, San Francisco, CA 94080 USA

[2] Calico Labs, San Francisco, CA 94080 USA

[3] Stanford Univ, Program Canc Biol, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[5] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA

[6] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA

[7] Genentech Inc, Dept Prot Sci, San Francisco, CA 94080 USA

[8] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA

[9] Unity Biotechnol, Brisbane, CA 94005 USA

[10] Genentech Inc, Dept Discovery Chem, San Francisco, CA 94080 USA

来源：

CELL REPORTS | 2018年 / 24卷 / 07期

关键词：

INHIBITOR; TRANSCRIPTION; PROTEIN;

D O I：

10.1016/j.celrep.2018.07.041

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin. Using this approach to dissect the role of H3K27Ac at enhancers, we identify a critical role for this modification in the production of enhancer RNAs and transcription of enhancer-regulated gene networks.

引用

页码：1722 / 1729

页数：8

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