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Open Access

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

Author Affiliations

  1. Xuan Pan1,
  2. Madhusudhan Papasani1,
  3. Yi Hao2,
  4. Marco Calamito2,
  5. Fang Wei1,
  6. William J Quinn2,
  7. Arindam Basu1,
  8. Junwen Wang3,
  9. Suchita Hodawadekar1,
  10. Kristina Zaprazna1,
  11. Huifei Liu4,
  12. Yang Shi4,
  13. David Allman2,
  14. Michael Cancro2 and
  15. Michael L Atchison (atchison{at}vet.upenn.edu)*,1
  1. 1 Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
  2. 2 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  3. 3 Department of Biochemistry, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
  4. 4 Department of Pathology, Harvard University, Boston, MA, USA
  1. * Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, USA. Tel.:+1 215 898 6428; Fax:+1 215 573 5189; E-mail: atchison{at}vet.upenn.edu

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.

  • Received August 9, 2012.
  • Accepted February 11, 2013.

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