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BET proteins are a key component of immunoglobulin gene expression.
- Source :
-
Epigenomics [Epigenomics] 2017 Apr; Vol. 9 (4), pp. 393-406. Date of Electronic Publication: 2017 Mar 21. - Publication Year :
- 2017
-
Abstract
- Aim: BET proteins have been shown to regulate gene expression including inflammatory genes.<br />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).<br />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.<br />Conclusion: Our results indicate that BET proteins including Brd4 play a crucial role regulation B-cell-specific gene expression and immunoglobulin production.
- Subjects :
- Animals
Azepines pharmacology
B-Lymphocytes drug effects
B-Lymphocytes metabolism
Cell Cycle Proteins
Cell Line
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Epigenesis, Genetic drug effects
Gene Expression Regulation drug effects
Heterocyclic Compounds, 4 or More Rings pharmacology
Humans
Immunoglobulin G metabolism
Mice
Organic Cation Transporter 2
Promoter Regions, Genetic drug effects
Triazoles pharmacology
Azepines administration & dosage
B-Lymphocytes cytology
Heterocyclic Compounds, 4 or More Rings administration & dosage
Immunoglobulin G genetics
Nuclear Proteins metabolism
Organic Cation Transport Proteins metabolism
Transcription Factors metabolism
Triazoles administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1750-192X
- Volume :
- 9
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Epigenomics
- Publication Type :
- Academic Journal
- Accession number :
- 28322577
- Full Text :
- https://doi.org/10.2217/epi-2016-0147