Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci

Magdalena Rother, Robert-jan Palstra, S Jhunjhunwala, Kevin Kester, Wilfred van Ijcken, Rudi Hendriks, Jacques Dongen, C Murre, Menno van Zelm

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Abstract

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. Ig kappa relocated from the nuclear lamina to central domains only at the proB cell stage, whereas, Ig. 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.
Original languageUndefined/Unknown
Pages (from-to)175-186
Number of pages12
JournalNucleic Acids Research
Volume44
Issue number1
DOIs
Publication statusPublished - 2016

Research programs

  • EMC MGC-02-13-02
  • EMC MGC-02-21-01
  • EMC MM-02-72-01
  • EMC MM-04-42-02

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