Epigenetic ontogeny of the Igk locus during B cell development.
To become accessible for rearrangement, the immunoglobulin kappa locus must undergo a series of epigenetic changes. This begins in pro-B cells with the relocation of both immunoglobulin kappa alleles from the periphery to the center of the nucleus. In pre-B cells, one allele became preferentially packaged into an active chromatin structure characterized by histone acetylation and methylation of histone H3 lysine 4, while the other allele was recruited to heterochromatin, where it was associated with heterochromatin protein-gamma and Ikaros. These events in cis made only one allele accessible to trans-acting factors, such as RelB, which mediated DNA demethylation, to facilitate rearrangement. These results suggest that early B lymphoid epigenetic changes generate differential structures that serve as the basis for allelic exclusion.
Goldmit
Maya
M
Department of Experimental Medicine, Hebrew University Medical School, Jerusalem 91120, Israel.
Ji
Yanhong
Y
Skok
Jane
J
Roldan
Esther
E
Jung
Steffen
S
Cedar
Howard
H
Bergman
Yehudit
Y
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D051740:Ikaros Transcription Factor; D007136:Immunoglobulins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D006570:Heterochromatin; D006657:Histones; C014609:IgK; D007136:Immunoglobulins; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051841:Transcription Factor RelB; D051740:Ikaros Transcription Factor; D004247:DNA