TY - JOUR
T1 - Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci
AU - Rother, Magdalena B.
AU - Palstra, Robert Jan
AU - Jhunjhunwala, Suchit
AU - van Kester, Kevin A. M.
AU - van IJcken, Wilfred F. J.
AU - Hendriks, Rudi W.
AU - van Dongen, Jacques J. M.
AU - Murre, Cornelis
AU - van Zelm, Menno C.
PY - 2016/1/8
Y1 - 2016/1/8
N2 - 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, Igk 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.
AB - 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, Igk 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.
UR - http://www.scopus.com/inward/record.url?scp=84959561757&partnerID=8YFLogxK
U2 - 10.1093/nar/gkv928
DO - 10.1093/nar/gkv928
M3 - Article
AN - SCOPUS:84959561757
SN - 0305-1048
VL - 44
SP - 175
EP - 186
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 1
ER -