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Publication : Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci.

First Author  Rother MB Year  2016
Journal  Nucleic Acids Res Volume  44
Issue  1 Pages  175-86
PubMed ID  26384565 Mgi Jnum  J:249601
Mgi Id  MGI:5922706 Doi  10.1093/nar/gkv928
Citation  Rother MB, et al. (2016) Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci. Nucleic Acids Res 44(1):175-86
abstractText  Progenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag(-/-) progenitor-B cells to determine whether Ig locus contraction or nuclear positioning is decisive for stepwise rearrangements. We found that both Ig loci were contracted in pro-B and pre-B cells. Igh relocated from the nuclear lamina to central domains only at the pro-B cell stage, whereas, Igkappa remained sequestered at the lamina, and only at the pre-B cell stage located to central nuclear domains. Finally, in vitro induced re-positioning of Ig alleles away from the nuclear periphery increased germline transcription of Ig loci in pre-pro-B cells. Thus, Ig locus contraction juxtaposes genomically distant elements to mediate efficient recombination, however, sequential positioning of Ig loci away from the nuclear periphery determines stage-specific accessibility of Ig loci.
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