B cell–specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers
B cell–specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers
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DOI：
10.1038/ni.1829
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发表时间：
2010-02
影响因子：
30.5
通讯作者：
T. Tran;Mikiyo Nakata;Keiichiro Suzuki;N. Begum;R. Shinkura;S. Fagarasan;T. Honjo;H. Nagaoka
中科院分区：
文献类型：
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作者：
T. Tran;Mikiyo Nakata;Keiichiro Suzuki;N. Begum;R. Shinkura;S. Fagarasan;T. Honjo;H. Nagaoka
激活诱导胞苷脱氨酶（AID）对抗体记忆的产生至关重要，但也针对癌基因和其他基因。我们研究了aida（编码AID）在类开关诱导的CH12F3-2细胞中的转录调控，发现aida的调控除了涉及5 '启动子区域外，还涉及多层正调控元件的抑制。5 '上游区域包含应答细胞因子信号的功能基序、共刺激分子CD40的配体或激活转录因子NF-κB的刺激。第一个内含子包含普遍存在的沉默子c-Myb和E2f以及B细胞特异性激活子Pax5和e -box结合蛋白的功能结合元件。我们的研究结果表明，aidais受B细胞特异性和刺激响应元件以及普遍存在的沉默子之间的平衡调节。
Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes, among other genes. We investigated the transcriptional regulation ofAicda(which encodes AID) in class switch–inducible CH12F3-2 cells and found thatAicdaregulation involved derepression by several layers of positive regulatory elements in addition to the 5′ promoter region. The 5′ upstream region contained functional motifs for the response to signaling by cytokines, the ligand for the costimulatory molecule CD40 or stimuli that activated the transcription factor NF-κB. The first intron contained functional binding elements for the ubiquitous silencers c-Myb and E2f and for the B cell–specific activator Pax5 and E-box-binding proteins. Our results show thatAicdais regulated by the balance between B cell–specific and stimulation-responsive elements and ubiquitous silencers.