Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development.
Immunoglobulin (Ig) loci are selectively activated for transcription and rearrangement during B lymphocyte development. Using fluorescence in situ hybridization, we show that Ig heavy (H) and Igkappa loci are preferentially positioned at the nuclear periphery in hematopoietic progenitors and pro-T cells but are centrally configured in pro-B nuclei. The inactive loci at the periphery do not associate with centromeric heterochromatin. Upon localization away from the nuclear periphery in pro-B cells, the IgH locus appears to undergo large-scale compaction. We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igkappa loci during lymphocyte development.
Kosak
Steven T
ST
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
Skok
Jane A
JA
Medina
Kay L
KL
Riblet
Roy
R
Le Beau
Michelle M
MM
Fisher
Amanda G
AG
Singh
Harinder
H
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000235:genetics* / Q000648:ultrastructure; D002503:Centromere / Q000737:chemistry / Q000235:genetics; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006570:Heterochromatin / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D019891:Leukopoiesis; D051379:Mice; D009685:Nuclear Envelope / Q000235:genetics; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D006570:Heterochromatin; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains