1. Academic Validation
  2. Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA

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

  • Mol Cell Biol. 2009 Mar;29(5):1375-87. doi: 10.1128/MCB.01365-08.
Bo Huang 1 Xiao-Dong Yang Ming-Ming Zhou Keiko Ozato Lin-Feng Chen
Affiliations

Affiliation

  • 1 Department of Biochemistry, College of Medicine, MC-714, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
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.

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