BET proteins are a key component of immunoglobulin gene expression. (April 2017)

• Record Type: Journal Article
• Authors: Shim, Jung Min; Lee, Jin S; Russell, Kirsty E; Wiegman, Coen H; Barnes, Peter J; Fear, David; Adcock, Ian M; Durham, Andrew L
• Is Part Of: Epigenomics. Volume 9:Number 4(2017)
• Page Start: 393
• Page End: 406
• Publication Date: 2017-04
• Subjects: B cells -- Brd4 -- bromo and extraterminal domains -- epigenetic gene regulation -- histone modifications -- immunoglobulin -- JQ1 -- Oct2; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2016-0147
• Languages: English
• ISSNs: 1750-1911

Abstract

Aim: BET proteins have been shown to regulate gene expression including inflammatory genes.Methods: In order to investigate the role of the BET proteins in immunoglobulin production we treated the human B-cell line CLNH11.4 and primary human B cells and ozone-exposed mice with BET inhibitors (JQ1 or IBET151).Results: Both proliferation and IgG production were reduced by JQ1 in a concentration-dependent manner. JQ1 significantly reduced immunoglobulin gene transcription. In vivo treatment of ozone-exposed mice with the BET inhibitor IBET151 similarly inhibited ozone-induced immunoglobulin production. JQ1 did not reduce the protein levels of Brd4 or Oct2 per se but reduced the ability of Brd4 and Oct2 to co-immunoprecipitate and of Oct2 to bind to immunoglobulin gene promoters.Conclusion: Our results indicate that BET proteins including Brd4 play a crucial role regulation B-cell-specific gene expression and immunoglobulin production.