Brd4 Coactivates Transcriptional Activation of NF-κB via Specific Binding to Acetylated RelA
Copyright policy )Brd4 Coactivates Transcriptional Activation of NF-κB via Specific Binding to Acetylated RelA
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.
- National Institute of Health Pakistan
- University of Illinois at Urbana–Champaign United States
- University of Illinois at Urbana Champaign United States
- National Institutes of Health United States
- Icahn School of Medicine at Mount Sinai United States
Transcriptional Activation, Binding Sites, Lysine, NF-kappa B, Transcription Factor RelA, Nuclear Proteins, Acetylation, Cell Cycle Proteins, DNA Polymerase II, Cyclin-Dependent Kinase 9, Cell Line, Mice, Animals, Humans, Protein Binding, Transcription Factors
Transcriptional Activation, Binding Sites, Lysine, NF-kappa B, Transcription Factor RelA, Nuclear Proteins, Acetylation, Cell Cycle Proteins, DNA Polymerase II, Cyclin-Dependent Kinase 9, Cell Line, Mice, Animals, Humans, Protein Binding, Transcription Factors
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