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Publication : A recombination silencer that specifies heterochromatin positioning and ikaros association in the immunoglobulin kappa locus.

First Author  Liu Z Year  2006
Journal  Immunity Volume  24
Issue  4 Pages  405-15
PubMed ID  16618599 Mgi Jnum  J:113347
Mgi Id  MGI:3665501 Doi  10.1016/j.immuni.2006.02.001
Citation  Liu Z, et al. (2006) A recombination silencer that specifies heterochromatin positioning and ikaros association in the immunoglobulin kappa locus. Immunity 24(4):405-15
abstractText  Allelic exclusion ensures that individual B lymphocytes produce only one kind of antibody molecule. Previous studies have shown that allelic exclusion of the mouse Igkappa locus occurs by the combination of monoallelic silencing and a low level of monoallelic activation for rearrangement combined with a negative feedback loop blocking additional functional rearrangements. Using yeast artificial chromosome-based single-copy isotransgenic mice, we have identified a cis-acting element that negatively regulates rearrangement in this locus, specifically in B cells. The element, termed Sis, resides in the V-J intervening sequence. Sis specifies the targeting of Igkappa transgenes in pre-B and B cells to centromeric heterochromatin and associates with Ikaros, a repressor protein that also colocalizes with centromeric heterochromatin. Significantly, these are hallmarks of silenced endogenous germline Igkappa genes in B cells. These results lead us to propose that Sis participates in the monoallelic silencing aspect of allelic exclusion regulation.
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