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BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones.

Abstract：

:Small-molecule BET inhibitors interfere with the epigenetic interactions between acetylated histones and the bromodomains of the BET family proteins, including BRD4, and they potently inhibit growth of malignant cells by targeting cancer-promoting genes. BRD4 interacts with the pause-release factor P-TEFb and has been proposed to release RNA polymerase II (Pol II) from promoter-proximal pausing. We show that BRD4 occupies widespread genomic regions in mouse cells and directly stimulates elongation of both protein-coding transcripts and noncoding enhancer RNAs (eRNAs), in a manner dependent on bromodomain function. BRD4 interacts with elongating Pol II complexes and assists Pol II in progression through hyperacetylated nucleosomes by interacting with acetylated histones via bromodomains. On active enhancers, the BET inhibitor JQ1 antagonizes BRD4-associated eRNA synthesis. Thus, BRD4 is involved in multiple steps of the transcription hierarchy, primarily by facilitating transcript elongation both at enhancers and on gene bodies independently of P-TEFb.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Kanno T,Kanno Y,LeRoy G,Campos E,Sun HW,Brooks SR,Vahedi G,Heightman TD,Garcia BA,Reinberg D,Siebenlist U,O'Shea JJ,Ozato K

doi

10.1038/nsmb.2912

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

1047-57

issue

12

eissn

1545-9993

issn

1545-9985

pii

nsmb.2912

journal_volume

21

pub_type

杂志文章

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