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. |