RAG1-mediated ubiquitylation of histone H3 is required for chromosomal V(D)J recombination
RAG1-mediated ubiquitylation of histone H3 is required for chromosomal V(D)J recombination
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DOI：
10.1038/cr.2015.1
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发表时间：
2015-02-01
期刊：
影响因子：
44.1
通讯作者：
Liu, Xiaolong
中科院分区：
文献类型：
--
作者：
Deng, Zimu;Liu, Haifeng;Liu, Xiaolong
RAG1和RAG2蛋白是V(D)J重组的关键成分。RAG1的核心区能够催化重组反应；然而，非核心RAG1的生物学功能在很大程度上仍不清楚。在这里，我们表明，在携带RAG1环手指保守半胱氨酸残基突变(C325Y)的小鼠模型中，V(D)J重组在切割步骤被取消，并且这一效应伴随着组蛋白H3的单一泛素化减少。进一步的分析表明，非泛素化的组蛋白H3通过与RAG1的N端218个氨基酸相互作用来抑制RAG1对染色质的作用。我们的数据为一个模型提供了证据，在该模型中，RAG1的环指结构域介导的组蛋白H3的泛素化触发RAG1的释放，从而允许其过渡到切割阶段。总而言之，我们的发现揭示了RAG1的非核心区促进了染色体V(D)J泛素化依赖的途径的重组。
RAG1 and RAG2 proteins are key components in V(D)J recombination. The core region of RAG1 is capable of catalyzing the recombination reaction; however, the biological function of non-core RAG1 remains largely unknown. Here, we show that in a murine-model carrying the RAG1 ring-finger conserved cysteine residue mutation (C325Y), V(D)J recombination was abrogated at the cleavage step, and this effect was accompanied by decreased mono-ubiquitylation of histone H3. Further analyses suggest that un-ubiquitylated histone H3 restrains RAG1 to the chromatin by interacting with the N-terminal 218 amino acids of RAG1. Our data provide evidence for a model in which ubiquitylation of histone H3 mediated by the ring-finger domain of RAG1 triggers the release of RAG1, thus allowing its transition into the cleavage phase. Collectively, our findings reveal that the non-core region of RAG1 facilitates chromosomal V(D)J recombination in a ubiquitylation-dependent pathway.