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

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. Ho...

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Autores principales: Song, Yawei, Hu, Gongcheng, Jia, Jinping, Yao, Mingze, Wang, Xiaoshan, Lu, Wenliang, Hutchins, Andrew P., Chen, Jiekai, Ozato, Keiko, Yao, Hongjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746802/
https://www.ncbi.nlm.nih.gov/pubmed/33344510
http://dx.doi.org/10.3389/fmolb.2020.618088
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author Song, Yawei
Hu, Gongcheng
Jia, Jinping
Yao, Mingze
Wang, Xiaoshan
Lu, Wenliang
Hutchins, Andrew P.
Chen, Jiekai
Ozato, Keiko
Yao, Hongjie
author_facet Song, Yawei
Hu, Gongcheng
Jia, Jinping
Yao, Mingze
Wang, Xiaoshan
Lu, Wenliang
Hutchins, Andrew P.
Chen, Jiekai
Ozato, Keiko
Yao, Hongjie
author_sort Song, Yawei
collection PubMed
description 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.
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spelling pubmed-77468022020-12-19 DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner Song, Yawei Hu, Gongcheng Jia, Jinping Yao, Mingze Wang, Xiaoshan Lu, Wenliang Hutchins, Andrew P. Chen, Jiekai Ozato, Keiko Yao, Hongjie Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2020-12-04 /pmc/articles/PMC7746802/ /pubmed/33344510 http://dx.doi.org/10.3389/fmolb.2020.618088 Text en Copyright © 2020 Song, Hu, Jia, Yao, Wang, Lu, Hutchins, Chen, Ozato and Yao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Song, Yawei
Hu, Gongcheng
Jia, Jinping
Yao, Mingze
Wang, Xiaoshan
Lu, Wenliang
Hutchins, Andrew P.
Chen, Jiekai
Ozato, Keiko
Yao, Hongjie
DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner
title DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner
title_full DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner
title_fullStr DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner
title_full_unstemmed DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner
title_short DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner
title_sort dna damage induces dynamic associations of brd4/p-tefb with chromatin and modulates gene transcription in a brd4-dependent and -independent manner
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746802/
https://www.ncbi.nlm.nih.gov/pubmed/33344510
http://dx.doi.org/10.3389/fmolb.2020.618088
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