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 Previous Article

Molecular and Cellular Biology, March 2009, p. 1375-1387, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.01365-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Brd4 Coactivates Transcriptional Activation of NF-{kappa}B via Specific Binding to Acetylated RelA {triangledown}

Bo Huang,1 Xiao-Dong Yang,1 Ming-Ming Zhou,2 Keiko Ozato,3 and Lin-Feng Chen1*

Department of Biochemistry, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801,1 Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029,2 Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 208923

Received 27 August 2008/ Returned for modification 29 September 2008/ Accepted 19 November 2008

Acetylation of the RelA subunit of NF-{kappa}B, especially at lysine-310, is critical for the transcriptional activation of NF-{kappa}B 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-{kappa}B and the expression of a subset of NF-{kappa}B-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-{kappa}B-dependent inflammatory genes. Our results identify Brd4 as a novel coactivator of NF-{kappa}B 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-{kappa}B and the NF-{kappa}B-dependent inflammatory response.

* Corresponding author. Mailing address: Department of Biochemistry, College of Medicine, MC-714, University of Illinois at Urbana-Champaign, Urbana, IL 61801. Phone: (217) 333-7764. Fax: (217) 244-5858. E-mail: lfchen{at}life.uiuc.edu

{triangledown} Published ahead of print on 22 December 2008.

Molecular and Cellular Biology, March 2009, p. 1375-1387, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.01365-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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