BET proteins are a key component of immunoglobulin gene expression

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Title: BET proteins are a key component of immunoglobulin gene expression
Author(s): Shim, JM
Lee, JS
Russell, KE
Wiegman, CS
Barnes, P
Fear, D
Adcock, IM
Durham, AL
Item Type: Journal Article
Abstract: Aims: Bromo and extraterminal domain (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. Conclusions: Our results indicate that BET proteins including Brd4 play a crucial role regulation B cell specific gene expression and immunoglobulin production.
Publication Date: 21-Mar-2017
Date of Acceptance: 8-Feb-2017
URI: http://hdl.handle.net/10044/1/44422
DOI: https://dx.doi.org/10.2217/epi-2016-0147
ISSN: 1750-192X
Publisher: Future Medicine
Start Page: 393
End Page: 406
Journal / Book Title: Epigenomics
Volume: 9
Issue: 4
Copyright Statement: © 2017 The Author(s). This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Medical Research Council (MRC)
Wellcome Trust
Funder's Grant Number: G0801266
093080/Z/10/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
B cells
Brd4
bromo and extraterminal domains
epigenetic gene regulation
histone modifications
immunoglobulin
JQ1
Oct2
OBSTRUCTIVE PULMONARY-DISEASE
BROMODOMAIN PROTEIN
BRD4
TRANSCRIPTION
CELLS
PROLIFERATION
REARRANGEMENT
INFLAMMATION
INHIBITION
ENHANCER
B cells
Brd4
JQ1
Oct2
bromo and extraterminal domains
epigenetic gene regulation
histone modifications
immunoglobulin
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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