Chromatin architecture near a potential 3′ end of the Igh locus involves modular regulation of histone modifications during B-Cell development and in vivo occupancy at CTCF sites
Chromatin architecture near a potential 3′ end of the Igh locus involves modular regulation of histone modifications during B-Cell development and in vivo occupancy at CTCF sites
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DOI：
10.1128/mcb.25.4.1511-1525.2005
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发表时间：
2005-02-01
影响因子：
5.3
通讯作者：
Birshtein, BK
中科院分区：
文献类型：
--
作者：
Garrett, FE;Emelyanov, AV;Birshtein, BK
小鼠的Igh位点在dna酶i超敏感位点有一个3‘调控区（3’ RR），包含4个增强子（hs3A、hs1、2、hs3B和hs4）。3′RR通过控制种系转录，对多种同型的类开关重组（class switch recombination， CSR）产生长期影响。通过染色质免疫沉淀测定乙酰化组蛋白H3和H4以及二甲基化H3 （K4）的水平，我们发现在b细胞发育的早期，包含3' RR增强子的染色质开始获得典型的开放构象的逐步修饰。hs4增强子最初在前B细胞和前B细胞中与活性染色质相关，然后在B细胞和浆细胞中与hs3A、hs1、hs2和hs3B相关。静息的脾B细胞和脂多糖诱导的脾B细胞发生CSR的历史修饰相似。从前b细胞阶段开始，hs4下游类似的11kb区域显示H3和H4修饰，表明染色质开放。该区域包含新发现的DNase i超敏位点和几个CTCF靶位点，其中一些在体内以发育调节的方式被占据。成熟B细胞中延伸的3' RR的开放染色质环境两侧是与组蛋白H3的二甲基化K9相关的区域。总之，这些数据表明，3' RR元件位于一个特定的染色质亚结构域中，该结构域中包含CTCF结合位点和发育调节模块。
The murine Igh locus has a 3' regulatory region (3' RR) containing four enhancers (hs3A, hs1,2, hs3B, and hs4) at DNase I-hypersensitive sites. The 3' RR exerts long-range effects on class switch recombination (CSR) to several isotypes through its control of germ line transcription. By measuring levels of acetylated histones H3 and H4 and of dimethylated H3 (K4) with chromatin immunoprecipitation assays, we found that early in B-cell development, chromatin encompassing the enhancers of the 3' RR began to attain stepwise modifications typical of an open conformation. The hs4 enhancer was associated with active chromatin initially in pro- and pre-B cells and then together with hs3A, hs1,2, and hs3B in B and plasma cells. Historic modifications were similar in resting splenic B cells and in splenic B cells induced by lipopolysaccharide to undergo CSR. From the pro-B-cell stage onward, the similar to11-kb region immediately downstream of hs4 displayed H3 and H4 modifications indicative of open chromatin. This region contained newly identified DNase I-hypersensitive sites and several CTCF target sites, some of which were occupied in vivo in a developmentally regulated manner. The open chromatin environment of the extended 3' RR in mature B cells was flanked by regions associated with dimethylated K9 of histone H3. Together, these data suggest that 3' RR elements are located within a specific chromatin subdomain that contains CTCF binding sites and developmentally regulated modules.