Maës Jérôme, Chappaz Stéphane, Cavelier Patricia, O'Neill Laura, Turner Bryan, Rougeon François, Goodhardt Michele
Unité de Génétique et Biochimie du Développement, Unité de Recherche Associée Centre National de la Recherche Scientifique 1960, Département d'Immunologie, Institut Pasteur, Paris, France.
J Immunol. 2006 May 1;176(9):5409-17. doi: 10.4049/jimmunol.176.9.5409.
IgH genes are assembled during early B cell development by a series of regulated DNA recombination reactions in which DH and JH segments are first joined followed by V(H) to DJH rearrangement. Recent studies have highlighted the role of chromatin structure in the control of V(D)J recombination. In this study, we show that, in murine pro-B cell precursors, the JH segments are located within a 6-kb DNase I-sensitive chromatin domain containing acetylated histones H3 and H4, which is delimited 5' by the DQ52 promoter element and 3' by the intronic enhancer. Within this domain, the JH segments are covered by phased nucleosomes. High-resolution mapping of nucleosomes reveals that, in pro-B cells, unlike recombination refractory nonlymphoid cells, the recombination signal sequences flanking the four JH segments are located in regions of enhanced micrococcal nuclease and restriction enzyme accessibility, corresponding to either nucleosome-free regions or DNA rendered accessible within a nucleosome. These results support the idea that nucleosome remodeling provides an additional level of control in the regulation of Ig locus accessibility to recombination factors in B cell precursors.
免疫球蛋白重链(IgH)基因在早期B细胞发育过程中通过一系列受调控的DNA重组反应进行组装,其中首先是重链多样性(DH)和连接片段(JH)连接,随后是重链可变区(V(H))与DJH重排。最近的研究强调了染色质结构在V(D)J重组控制中的作用。在本研究中,我们发现,在小鼠前B细胞前体中,JH片段位于一个6 kb的对脱氧核糖核酸酶I敏感的染色质结构域内,该结构域含有乙酰化组蛋白H3和H4,其5'端由DQ52启动子元件界定,3'端由内含子增强子界定。在这个结构域内,JH片段被相位核小体覆盖。核小体的高分辨率图谱显示,在前B细胞中,与重组难治性非淋巴细胞不同,四个JH片段侧翼的重组信号序列位于微球菌核酸酶和限制酶可及性增强的区域,对应于无核小体区域或核小体内可及的DNA。这些结果支持这样一种观点,即核小体重塑在B细胞前体中Ig基因座对重组因子的可及性调控中提供了额外的控制水平。