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J Biol Chem. 2018 Apr 6;293(14):4993-5004. doi: 10.1074/jbc.RA117.001518. Epub 2018 Feb 20.

Bromodomain-containing protein 4-independent transcriptional activation by autoimmune regulator (AIRE) and NF-κB.

Author information

1
From the Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, California 94143.
2
From the Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, California 94143 matija.peterlin@ucsf.edu.

Abstract

Autoimmune regulator (AIRE) and nuclear factor-κB (NF-κB) are transcription factors (TFs) that direct the expression of individual genes and gene clusters. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that recognizes and binds to acetylated histones. BRD4 also has been reported to promote interactions between the positive transcription elongation factor b (P-TEFb) and AIRE or P-TEFb and NF-κB subunit p65. Here, we report that AIRE and p65 bind to P-TEFb independently of BRD4. JQ1, a compound that disrupts interactions between BRD4 and acetylated proteins, does not decrease transcriptional activities of AIRE or p65. Moreover, siRNA-mediated inactivation of BRD4 alone or in combination with JQ1 had no effects on AIRE- and NF-κB-targeted genes on plasmids and in chromatin and on interactions between P-TEFb and AIRE or NF-κB. Finally, ChIP experiments revealed that recruitment of P-TEFb to AIRE or p65 to transcription complexes was independent of BRD4. We conclude that direct interactions between AIRE, NF-κB, and P-TEFb result in efficient transcription of their target genes.

KEYWORDS:

NF-kB transcription factor; bromodomain-containing protein 4; chromatin; epigenetic regulation; gene expression; gene transcription; transcription factor; transcription promoter

PMID:
29463681
PMCID:
PMC5892592
[Available on 2019-04-06]
DOI:
10.1074/jbc.RA117.001518
[Indexed for MEDLINE]

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