Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination.
Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination.
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DOI：
10.1084/jem.20101136
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发表时间：
2010-12-20
期刊：
影响因子：
--
通讯作者：
Schatz DG
中科院分区：
文献类型：
--
作者：
Ji Y;Little AJ;Banerjee JK;Hao B;Oltz EM;Krangel MS;Schatz DG
RAG 1与TCR基因元件的结合是由转录控制元件和转录本身决定的;这些发现直接证实了长期以来的可及性模型。在淋巴细胞发育过程中，V（D）J重组以明确的顺序组装抗原受体基因。这种顺序过程长期以来一直在可及性模型的背景下被理解，该模型指出，V（D）J重组是通过控制重组机制接近其染色体底物的能力来调节的。事实上，“开放”染色质的许多特征与V（D）J重组相关，并且启动子和增强子强烈地涉及在相邻染色质中产生重组酶可接近的构型。可及性模型的一个重要预测是顺式元件和转录控制重组激活基因1（RAG 1）和RAG 2蛋白与其DNA靶的结合。然而，这一预测尚未得到直接验证。在这项研究中，我们使用突变的Tcra和Tcrb等位基因来证明增强子控制RAG 1在Jα或Dβ/Jβ基因片段的全局结合，启动子和转录局部指导RAG 1结合，并且RAG 1结合可以在RAG 2不存在的情况下靶向。这些发现揭示了调节RAG结合的遗传机制的重要特征，并直接证实了可及性模型。
RAG1 binding to TCR gene elements is dictated by transcriptional control elements and by transcription itself; these findings provide direct confirmation of the long-held accessibility model. V(D)J recombination assembles antigen receptor genes in a well-defined order during lymphocyte development. This sequential process has long been understood in the context of the accessibility model, which states that V(D)J recombination is regulated by controlling the ability of the recombination machinery to gain access to its chromosomal substrates. Indeed, many features of “open” chromatin correlate with V(D)J recombination, and promoters and enhancers have been strongly implicated in creating a recombinase-accessible configuration in neighboring chromatin. An important prediction of the accessibility model is that cis-elements and transcription control binding of the recombination-activating gene 1 (RAG1) and RAG2 proteins to their DNA targets. However, this prediction has not been tested directly. In this study, we use mutant Tcra and Tcrb alleles to demonstrate that enhancers control RAG1 binding globally at Jα or Dβ/Jβ gene segments, that promoters and transcription direct RAG1 binding locally, and that RAG1 binding can be targeted in the absence of RAG2. These findings reveal important features of the genetic mechanisms that regulate RAG binding and provide a direct confirmation of the accessibility model.
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影响因子：
32.4
作者：
Whitehurst, CE;Chattopadhyay, S;Chen, JZ
通讯作者：
Chen, JZ
影响因子：
64.5
作者：
StanhopeBaker, P;Hudson, KM;Schlissel, MS
通讯作者：
Schlissel, MS
影响因子：
32.4
作者：
Liu, Yun;Subrahmanyam, Ramesh;Desiderio, Stephen
通讯作者：
Desiderio, Stephen
DOI：
10.1084/jem.192.5.625
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mathieu N;Hempel WM;Spicuglia S;Verthuy C;Ferrier P
通讯作者：
Ferrier P
影响因子：
32.4
作者：
Sleckman, BP;Bardon, CG;Alt, FW
通讯作者：
Alt, FW