Activation of V(D)J recombination at the IgH chain JH locus occurs within a 6-kilobase chromatin domain and is associated with nucleosomal remodeling.
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.
Maës
Jérôme
J
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.
Chappaz
Stéphane
S
Cavelier
Patricia
P
O'Neill
Laura
L
Turner
Bryan
B
Rougeon
François
F
Goodhardt
Michele
M
D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics*; D004274:DNA, Recombinant / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D015321:Gene Rearrangement; D006657:Histones / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics
D002843:Chromatin; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D006657:Histones; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D009707:Nucleosomes; C499308:Rag2 protein, mouse; D004720:Endonucleases