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PMID: 19103749 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA.

Molecular and cellular biology ·Vol. 29 ·No. 5 ·2009-03-00 ·Pages 1375-87

Huang B, Yang XD, Zhou MM, Ozato K, Chen LF

Abstract

Acetylation of the RelA subunit of NF-kappaB, especially at lysine-310, is critical for the transcriptional activation of NF-kappaB and the expression of inflammatory genes. In this study, we demonstrate that bromodomains of Brd4 bind to acetylated lysine-310. Brd4 enhances transcriptional activation of NF-kappaB and the expression of a subset of NF-kappaB-responsive inflammatory genes in an acetylated lysine-310-dependent manner. Bromodomains of Brd4 and acetylated lysine-310 of RelA are both required for the mutual interaction and coactivation function of Brd4. Finally, we demonstrate that Brd4 further recruits CDK9 to phosphorylate C-terminal domain of RNA polymerase II and facilitate the transcription of NF-kappaB-dependent inflammatory genes. Our results identify Brd4 as a novel coactivator of NF-kappaB through specifically binding to acetylated lysine-310 of RelA. In addition, these studies reveal a mechanism by which acetylated RelA stimulates the transcriptional activity of NF-kappaB and the NF-kappaB-dependent inflammatory response.

MeSH Terms
Acetylation Animals Binding Sites Cell Cycle Proteins Cell Line Cyclin-Dependent Kinase 9/metabolism DNA Polymerase II/metabolism Humans Lysine Mice NF-kappa B/metabolism Nuclear Proteins/metabolism Protein Binding Transcription Factor RelA/metabolism Transcription Factors/metabolism Transcriptional Activation
Chemicals
BRD4 protein, human Brd4 protein, mouse Cell Cycle Proteins NF-kappa B Nuclear Proteins Transcription Factor RelA Transcription Factors Cyclin-Dependent Kinase 9 DNA Polymerase II Lysine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Huang Bo
Department of Biochemistry, College of Medicine, MC-714, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Yang Xiao-Dong
Zhou Ming-Ming
Ozato Keiko
Chen Lin-Feng
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01365-08
Published
2009-03-00
Epub
2008-00-22
Pages
1375-87
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2643823
Subset
IM
Grants
NIDDK NIH HHS · R01 DK085158 · United States
External Links
PubMed source DOI: 10.1128/MCB.01365-08 PMC Full Text View journal details
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