Immunoglobulin class-switch DNA recombination: induction, targeting and beyond.

Immunoglobulin class-switch DNA recombination: induction, targeting and beyond.
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DOI:
10.1038/nri3216
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发表时间:
2012-06-25
期刊:
Nature reviews. Immunology
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免疫球蛋白重链(IgH)基因座的类别转换DNA重组(CSR)对抗体应答的成熟至关重要,并且非常需要AID胞苷脱氨酶。CSR需要染色质状态的改变和IgH基因座上游和下游开关(S)区域的转录激活,所述开关(S)区域将经历S-S DNA重组、AID的诱导以及通过14-3-3衔接子将CSR因子靶向至S区域,并且如通过转录机制和组蛋白修饰所实现的。在这篇综述中,我们重点介绍了CSR诱导和靶向的最新进展。我们还概述了一个集成的模型组装的大分子复合物的关键表观遗传信息的CSR机制的酶效应。
Class switch DNA recombination (CSR) of the immunoglobulin heavy chain (IgH) locus is central to the maturation of the antibody response and critically requires the AID cytidine deaminase. CSR entails changes of the chromatin state and transcriptional activation of the IgH locus upstream and downstream switch (S) regions that are to undergo S-S DNA recombination, induction of AID, and targeting of CSR factors to S regions by 14-3-3 adaptors and as enabled by the transcription machinery and histone modifications. In this Review, we focus on recent advances in CSR induction and targeting. We also outline an integrated model of the assembly of macromolecular complexes that transduce critical epigenetic information to enzymatic effectors of the CSR machinery.
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