溴结构域和超末端结构域（BET）蛋白是免疫球蛋白基因表达的关键组成部分。
BET proteins are a key component of immunoglobulin gene expression.
作者信息
Shim Jung Min, Lee Jin S, Russell Kirsty E, Wiegman Coen H, Barnes Peter J, Fear David, Adcock Ian M, Durham Andrew L
机构信息
Airways Disease Section, National Heart & Lung Institute, Imperial College London, London, SW7 2AZ, UK.
MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Department of Respiratory Medicine & Allergy, King's College London, London, WC2R 2LS, UK.
出版信息
Epigenomics. 2017 Apr;9(4):393-406. doi: 10.2217/epi-2016-0147. Epub 2017 Mar 21.
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.
目的
已有研究表明BET蛋白可调节包括炎症基因在内的基因表达。
方法
为了研究BET蛋白在免疫球蛋白产生中的作用，我们用BET抑制剂（JQ1或IBET151）处理人B细胞系CLNH11.4、原代人B细胞以及暴露于臭氧的小鼠。
结果
JQ1以浓度依赖的方式降低了增殖和IgG产生。JQ1显著降低了免疫球蛋白基因转录。用BET抑制剂IBET151对暴露于臭氧的小鼠进行体内治疗同样抑制了臭氧诱导的免疫球蛋白产生。JQ1本身并未降低Brd4或Oct2的蛋白水平，但降低了Brd4和Oct2共免疫沉淀的能力以及Oct2与免疫球蛋白基因启动子结合的能力。
结论
我们的结果表明，包括Brd4在内的BET蛋白在调节B细胞特异性基因表达和免疫球蛋白产生中起关键作用。
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