YY1 controls Igκ repertoire and B-cell development, and localizes with condensin on the Igκ locus

Xuan Pan, Madhusudhan Papasani, Yi Hao, Marco Calamito, Fang Wei, William J. Quinn, Arindam Basu, Junwen Wang, Suchita Hodawadekar, Kristina Zaprazna, Huifei Liu, Yang Shi, David Allman, Michael Cancro, Michael L. Atchison

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Conditional knock-out (KO) of Polycomb Group (PcG) protein YY1 results in pro-B cell arrest and reduced immunoglobulin locus contraction needed for distal variable gene rearrangement. The mechanisms that control these crucial functions are unknown. We deleted the 25 amino-acid YY1 REPO domain necessary for YY1 PcG function, and used this mutant (YY1ΔREPO), to transduce bone marrow from YY1 conditional KO mice. While wild-type YY1 rescued B-cell development, YY1ΔREPO failed to rescue the B-cell lineage yielding reduced numbers of B lineage cells. Although the IgH rearrangement pattern was normal, there was a selective impact at the Igκ locus that showed a dramatic skewing of the expressed Igκ repertoire. We found that the REPO domain interacts with proteins from the condensin and cohesin complexes, and that YY1, EZH2 and condensin proteins co-localize at numerous sites across the Ig kappa locus. Knock-down of a condensin subunit protein or YY1 reduced rearrangement of Igκ Vκ genes suggesting a direct role for YY1-condensin complexes in Igκ locus structure and rearrangement.

Original languageEnglish (US)
Pages (from-to)1168-1182
Number of pages15
JournalEMBO Journal
Volume32
Issue number8
DOIs
StatePublished - Apr 17 2013

Keywords

  • B-cell development
  • Polycomb
  • YY1
  • immunoglobulin
  • rearrangement

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Pan, X., Papasani, M., Hao, Y., Calamito, M., Wei, F., Quinn, W. J., Basu, A., Wang, J., Hodawadekar, S., Zaprazna, K., Liu, H., Shi, Y., Allman, D., Cancro, M., & Atchison, M. L. (2013). YY1 controls Igκ repertoire and B-cell development, and localizes with condensin on the Igκ locus. EMBO Journal, 32(8), 1168-1182. https://doi.org/10.1038/emboj.2013.66