Chromatin remodeling at the Ig loci prior to V(D)J recombination.
Rearrangement of Ig H and L chain genes is highly regulated and takes place sequentially during B cell development. Several lines of evidence indicate that chromatin may modulate accessibility of the Ig loci for V(D)J recombination. In this study, we show that remodeling of V and J segment chromatin occurs before V(D)J recombination at the endogenous H and kappa L chain loci. In recombination-activating gene-deficient pro-B cells, there is a reorganization of nucleosomal structure over the H chain J(H) cluster and increased DNase I sensitivity of V(H) and J(H) segments. The pro-B/pre-B cell transition is marked by a decrease in the DNase I sensitivity of V(H) segments and a reciprocal increase in the nuclease sensitivity of Vkappa and Jkappa segments. In contrast, J(H) segments remain DNase I sensitive, and their nucleosomal organization is maintained in mu(+) recombination-activating gene-deficient pre-B cells. These results indicate that initiation of rearrangement is associated with changes in the chromatin structure of both V and J segments, whereas stopping recombination involves changes in only V segment chromatin. We further find an increase in histone H4 acetylation at both the H and kappa L chain loci at the pro-B cell stage. Although histone H4 acetylation appears to be an early change associated with B cell commitment, acetylation alone is not sufficient to promote subsequent modifications in Ig chromatin.
Maës
J
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.
O'Neill
L P
LP
Cavelier
P
P
Turner
B M
BM
Rougeon
F
F
Goodhardt
M
M
D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002461:Cell Line, Transformed; D002843:Chromatin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000187:drug effects; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000187:drug effects; D005803:Genes, Immunoglobulin / Q000187:drug effects; D005819:Genetic Markers / Q000276:immunology; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000276:immunology; D013234:Stem Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002843:Chromatin; D005819:Genetic Markers; D006657:Histones; D006877:Hydroxamic Acids; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D008070:Lipopolysaccharides; D009707:Nucleosomes; C012589:trichostatin A; D003850:Deoxyribonuclease I