BET proteins are a key component of immunoglobulin gene expression.
BET proteins have been shown to regulate gene expression including inflammatory genes.



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).



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.



Our results indicate that BET proteins including Brd4 play a crucial role regulation B-cell-specific gene expression and immunoglobulin production.
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Jung Min
JM
Shim
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Jin S
JS
Lee
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Kirsty E
KE
Russell
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Coen H
CH
Wiegman
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Peter J
PJ
Barnes
MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Department of Respiratory Medicine & Allergy, King's College London, London, WC2R 2LS, UK.
David
D
Fear
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Ian M
IM
Adcock
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Andrew L
AL
Durham
D000818:Animals; D001381:Azepines / Q000008:administration & dosage* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D000075102:Organic Cation Transporter 2; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism*; D014230:Triazoles / Q000008:administration & dosage* / Q000494:pharmacology; D000092468:Bromodomain Containing Proteins
D001381:Azepines; D018797:Cell Cycle Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D007074:Immunoglobulin G; D009687:Nuclear Proteins; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D014157:Transcription Factors; D014230:Triazoles; C561695:(+)-JQ1 compound; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C568713:GSK1210151A; C491013:SLC22A2 protein, human
B cells; Brd4; JQ1; Oct2; bromo and extraterminal domains; epigenetic gene regulation; histone modifications; immunoglobulin