A Recombination Silencer that Specifies Heterochromatin Positioning and Ikaros Association in the Immunoglobulin κ Locus

Zhe Liu, Piotr Widlak, Ying Zou, Fei Xiao, Misook Oh, Shuyu Li, Mee Young Chang, Jerry W. Shay, William T. Garrard

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Allelic exclusion ensures that individual B lymphocytes produce only one kind of antibody molecule. Previous studies have shown that allelic exclusion of the mouse Igκ 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 Igκ 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 Igκ genes in B cells. These results lead us to propose that Sis participates in the monoallelic silencing aspect of allelic exclusion regulation.

Original languageEnglish (US)
Pages (from-to)405-415
Number of pages11
JournalImmunity
Volume24
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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