Association between the Igk and Igh immunoglobulin loci mediated by the 3' Igk enhancer induces 'decontraction' of the Igh locus in pre-B cells.
Variable-(diversity)-joining (V(D)J) recombination at loci encoding the immunoglobulin heavy chain (Igh) and immunoglobulin light chain (Igk) takes place sequentially during successive stages in B cell development. Using three-dimensional DNA fluorescence in situ hybridization, here we identify a lineage-specific and stage-specific interchromosomal association between these two loci that marks the transition between Igh and Igk recombination. Colocalization occurred between pericentromerically located alleles in pre-B cells and was mediated by the 3' Igk enhancer. Deletion of this regulatory element prevented association of the Igh and Igk loci, inhibited pericentromeric recruitment and locus 'decontraction' of an Igh allele, and resulted in greater distal rearrangement of the gene encoding the variable heavy-chain region. Our data indicate involvement of the Igk locus and its 3' enhancer in directing the Igh locus to a repressive nuclear subcompartment and inducing the Igh locus to decontract.
Hewitt
Susannah L
SL
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
Farmer
Deborah
D
Marszalek
Katarzyna
K
Cadera
Emily
E
Liang
Hong-Erh
HE
Xu
Yang
Y
Schlissel
Mark S
MS
Skok
Jane A
JA
D024509:3' Flanking Region / Q000235:genetics; D000818:Animals; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D050438:Genes, Immunoglobulin Heavy Chain / Q000502:physiology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007136:Immunoglobulins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism; D011995:Recombination, Genetic
C014609:IgK; D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins