Attracting AID to targets of somatic hypermutation.
Attracting AID to targets of somatic hypermutation.
复制标题
将 AID 吸引到体细胞超突变的目标。
DOI：
10.1084/jem.20090821
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Storb,Ursula
中科院分区：
文献类型：
--
作者：
Tanaka,Atsushi;Shen,HongMing;Ratnam,Sarayu;Kodgire,Prashant;Storb,Ursula
免疫球蛋白（IG）基因的体细胞超突变（SHM）过程需要激活诱导的胞苷脱氨酶（AID）。虽然AID的错误定位对基因组完整性有害，但机制和负责靶向AID的顺式元件在很大程度上是未知的。我们发现，在IG增强子的背景下，三个CAGGTG顺式元件足以将SHM靶向附近的转录基因。CAGGTG基序结合突变细胞核提取物中的E47。在没有任何其他E47结合位点的构建体中用AAGGTG替换CAGGTG消除了SHM。CA与AA效应需要AID。CAGGTG不增强转录、染色质乙酰化或总体靶基因活性。单独的IG增强子的其他顺式元件不能吸引SHM机制。与其他最近的研究结果，我们假设，艾滋病的目标是在突变的B细胞表达的所有基因，在适当的情况下与CAGGTG基序。IG基因是最高度突变的基因，这大概是因为IG基因内的多个CAGGTG基序、高转录活性以及IG增强子中其他协作元件的存在。小洁org/misc/terms. shtml）。六个月后，它可以在知识共享许可证（署名-非商业性使用-相同方式共享3.0未移植许可证）下使用，如http：//creativecommons所述。org/licenses/by-nc-sa/3.0/）。
The process of somatic hypermutation (SHM) of immunoglobulin (Ig) genes requires activation-induced cytidine deaminase (AID). Although mistargeting of AID is detrimental to genome integrity, the mechanism and the cis-elements responsible for targeting of AID are largely unknown. We show that three CAGGTG cis-elements in the context of Ig enhancers are sufficient to target SHM to a nearby transcribed gene. The CAGGTG motif binds E47 in nuclear extracts of the mutating cells. Replacing CAGGTG with AAGGTG in the construct without any other E47 binding site eliminates SHM. The CA versus AA effect requires AID. CAGGTG does not enhance transcription, chromatin acetylation, or overall target gene activity. The other cis-elements of Ig enhancers alone cannot attract the SHM machinery. Collectively with other recent findings, we postulate that AID targets all genes expressed in mutating B cells that are associated with CAGGTG motifs in the appropriate context. Ig genes are the most highly mutated genes, presumably because of multiple CAGGTG motifs within the Ig genes, high transcription activity, and the presence of other cooperating elements in Ig enhancers.© 2010 Tanaka et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www. jem. org/misc/terms. shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons. org/licenses/by-nc-sa/3.0/).