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

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 (YY1 Delta REPO), to transduce bone marrow from YY1 conditional KO mice. While wild-type YY1 rescued B-cell development, YY1 Delta REPO 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 Ig kappa locus that showed a dramatic skewing of the expressed Ig kappa 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 Ig kappa V kappa genes suggesting a direct role for YY1-condensin complexes in Ig kappa locus structure and rearrangement. The EMBO Journal (2013) 32, 1168-1182. doi: 10.1038/emboj.2013.66; Published online 26 March 2013