nature-immunology201212-7

在V(D)J重组过程中,Igh位点发生精确有序的基因重排。来自美国国立卫生研究院国家老年研究所的Sen 及其同事发现DJH连接通过高度地局部性表观遗传修饰,招募并限制RAG重组酶,从而使得DH相关的重组信号序列起始第二步的Igh基因组装。相关的研究论文于10月28日在线发表在《Nature Immunology》期刊上。

-2012年12月《自然-免疫》

中文翻译


【题目】DH重组限制重组酶结合到DJH

【译文】免疫球蛋白的重链编码基因(Igh)的组装需要可变性(VH)、多样性(DH)和连接区(JH)基因片段的重排。三个关键的限制条件控制了VH的重组。这包括定时(VH重组紧随DH重组)、精确(VH基因片段仅与DJH连接结合)和等位基因专一性(VH重组仅发生在DJH重组等位基因中)。本研究提出了一个描述VH重组全面特性的模型。对DJH重组等位基因的分析表明,DJH连接被选择性地表观遗传标记,变得对核酸酶敏感,再与RAG重组酶蛋白结合,因此允许DH相关的重组信号序列起始第二步的Igh基因组装。本研究认为VH重组是精确的,因为这些重组没有延伸到定位于DJH连接5′端的种系DH片段中。

英文原稿


[Title]: Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions 

[Authors]:: Ramesh Subrahmanyam, Hansen Du, Irina Ivanova, Tirtha Chakraborty, Yanhong Ji, Yu Zhang, Frederick W Alt, David G Schatz & Ranjan Sen

[Abstract]: Genes encoding immunoglobulin heavy chains (Igh) are assembled by rearrangement of variable (VH), diversity (DH) and joining (JH) gene segments. Three critical constraints govern VH recombination. These include timing (VH recombination follows DH recombination), precision (VH gene segments recombine only to DJH junctions) and allele specificity (VH recombination is restricted to DJH-recombined alleles). Here we provide a model for these universal features of VH recombination. Analyses of DJH-recombined alleles showed that DJH junctions were selectively epigenetically marked, became nuclease sensitive and bound RAG recombinase proteins, which thereby permitted DH-associated recombination signal sequences to initiate the second step of Igh gene assembly. We propose that VH recombination is precise, because these changes did not extend to germline DH segments located 5′ of the DJH junction.

原文地址

http://www.nature.com/ni/journal/v13/n12/full/ni.2447.html

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