Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4
Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4
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DOI：
10.1073/pnas.1932643100
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发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Oettinger, MA
中科院分区：
文献类型：
--
作者：
Morshead, KB;Ciccone, DN;Oettinger, MA
在抗原受体装配的最早阶段，IG重链和T细胞受体β基因座的D和J区段分别在B和T细胞中重组，而V区段则不重组。不同的组蛋白修饰和核小体重塑因子BRG 1的不同分布模式被发现在“活性”（DJ）和“非活性”（V）区域。在赖氨酸4处二甲基化的组蛋白H3（二-Me H3-K4）的醒目“热点”位于IG重链和T细胞受体β基因座的活性DJ结构域的末端。BRG 1不定位于特定序列，因为它是与转录起始，而是与整个活性位点的模式，反映乙酰化组蛋白H3。在一些由H3-K9二甲基化标记的非活性位点内，在非随机基因片段特异性模式中发现两种不同水平的甲基化。我们认为di-Me H3-K4的热点是基因座可及性的重要标志。修饰的特定模式意味着V（D）J重组的调节涉及以局部方式募集特定的甲基转移酶。
In the earliest stages of antigen receptor assembly, D and J segments of the Ig heavy chain and T cell receptor beta loci are recombined in B and T cells, respectively, whereas the V segments are not. Distinct distribution patterns of various histone modifications and the nucleosome-remodeling factor BRG1 are found at "active" (DJ) and "inactive" (V) regions. Striking "hotspots" of histone H3 dimethylated at lysine 4 (di-Me H3-K4) are localized at the ends of the active DJ domains of both the Ig heavy chain and T cell receptor beta loci. BRG1 is not localized to specific sequences, as it is with transcriptional initiation, but rather associates with the entire active locus in a pattern that mirrors acetylation of histone H3. Within some inactive loci marked by H3-K9 dimethylation, two distinct levels of methylation are found in a nonrandom gene-segment-specific pattern. We suggest that the hotspots of di-Me H3-K4 are important marks for locus accessibility. The specific patterns of modification imply that the regulation of V(D)J recombination involves recruitment of specific methyltransferases in a localized manner.