Open AccessBrd4 Coactivates Transcriptional Activation of NF-κB via Specific Binding to Acetylated RelA
Author(s) -
Bo Huang,
Xiaodong Yang,
Ming Zhou,
Keiko Ozato,
Lin Feng Chen
Publication year - 2009
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01365-08
Subject(s) - bromodomain , brd4 , acetylation , biology , p300 cbp transcription factors , lysine , transcription factor , coactivator , rna polymerase ii , nf κb , microbiology and biotechnology , transcriptional regulation , regulation of gene expression , protein subunit , gene expression , gene , biochemistry , promoter , signal transduction , amino acid , histone acetyltransferases
Acetylation of the RelA subunit of NF-κB, especially at lysine-310, is critical for the transcriptional activation of NF-κB 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-κB and the expression of a subset of NF-κB-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-κB-dependent inflammatory genes. Our results identify Brd4 as a novel coactivator of NF-κB 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-κB and the NF-κB-dependent inflammatory response.