DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner

被引：6

作者：

Song, Yawei ^{[1
,2
,3
,4
,5
]}

Hu, Gongcheng ^{[2
,3
,4
,5
]}

Jia, Jinping ^{[2
]}

Yao, Mingze ^{[2
]}

Wang, Xiaoshan ^{[2
]}

Lu, Wenliang ^{[2
]}

Hutchins, Andrew P. ^{[6
]}

Chen, Jiekai ^{[2
,3
,5
]}

Ozato, Keiko ^{[7
]}

Yao, Hongjie ^{[2
,3
,4
,5
]}

机构：

[1] Univ Sci & Technol China, Sch Life Sci, Hefei, Peoples R China

[2] Guangzhou Med Univ, Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol,Joint Sch Life Sci, Guangzhou, Peoples R China

[3] Guangzhou Regenerat Med & Hlth GuangDong Lab, Bioland Lab, Guangzhou, Peoples R China

[4] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China

[5] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou, Peoples R China

[6] Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China

[7] NICHHD, Div Dev Biol, Bethesda, MD 20892 USA

来源：

FRONTIERS IN MOLECULAR BIOSCIENCES | 2020年 / 7卷

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

BRD4; P-TEFb; gene transcription; UV stress; JNK pathway; RNA-POLYMERASE-II; BROMODOMAIN PROTEIN BRD4; P-TEFB; INHIBITION; PHOSPHORYLATION; ELONGATION; RELEASE; POTENT;

D O I：

10.3389/fmolb.2020.618088

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The bromodomain-containing protein BRD4 has been thought to transmit epigenetic information across cell divisions by binding to both mitotic chromosomes and interphase chromatin. UV-released BRD4 mediates the recruitment of active P-TEFb to the promoter, which enhances transcriptional elongation. However, the dynamic associations between BRD4 and P-TEFb and BRD4-mediated gene regulation after UV stress are largely unknown. In this study, we found that BRD4 dissociates from chromatin within 30 min after UV treatment and thereafter recruits chromatin. However, P-TEFb binds tightly to chromatin right after UV treatment, suggesting that no interactions occur between BRD4 and P-TEFb within 30 min after UV stress. BRD4 knockdown changes the distribution of P-TEFb among nuclear soluble and chromatin and downregulates the elongation activity of RNA polymerase II. Inhibition of JNK kinase but not other MAP kinases impedes the interactions between BRD4 and P-TEFb. RNA-seq and ChIP assays indicate that BRD4 both positively and negatively regulates gene transcription in cells treated with UV stress. These results reveal previously unrecognized dynamics of BRD4 and P-TEFb after UV stress and regulation of gene transcription by BRD4 acting as either activator or repressor in a context-dependent manner.

引用

页数：12