Institute for Immunology and Department of Medicine, School of Medicine, University of California, Irvine, California 92697-4120, USA.
Nat Rev Immunol. 2012 Jun 25;12(7):517-31. doi: 10.1038/nri3216.
Class-switch DNA recombination (CSR) of the immunoglobulin heavy chain (IGH) locus is central to the maturation of the antibody response and crucially requires the cytidine deaminase AID. CSR involves changes in the chromatin state and the transcriptional activation of the IGH locus at the upstream and downstream switch (S) regions that are to undergo S-S DNA recombination. In addition, CSR involves the induction of AID expression and the targeting of CSR factors to S regions by 14-3-3 adaptors, and it is facilitated by the transcription machinery and by histone modifications. In this Review, we focus on recent advances regarding the induction and targeting of CSR and outline an integrated model of the assembly of macromolecular complexes that transduce crucial epigenetic information to enzymatic effectors of the CSR machinery.
类别转换 DNA 重组(CSR)的免疫球蛋白重链(IGH)基因座是成熟的抗体反应的核心,这需要胞嘧啶脱氨酶 AID。CSR 涉及在染色质状态的变化和 IGH 基因座在上游和下游开关(S)区域的转录激活,这些区域将经历 S-S DNA 重组。此外,CSR 涉及 AID 表达的诱导和 CSR 因子通过 14-3-3 衔接蛋白靶向 S 区域,并且由转录机制和组蛋白修饰来促进。在这篇综述中,我们重点介绍 CSR 的诱导和靶向的最新进展,并概述了一个整合模型,用于组装将关键表观遗传信息转导到 CSR 机制的酶效应物的大分子复合物。