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YY1 controls Igκ repertoire and B‐cell development, and localizes with condensin on the Igκ locus
Author(s) -
Pan Xuan,
Papasani Madhusudhan,
Hao Yi,
Calamito Marco,
Wei Fang,
Quinn William J,
Basu Arindam,
Wang Junwen,
Hodawadekar Suchita,
Zaprazna Kristina,
Liu Huifei,
Shi Yang,
Allman David,
Cancro Michael,
Atchison Michael L
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.66
Subject(s) - biology , repertoire , genetics , locus (genetics) , microbiology and biotechnology , gene , computational biology , physics , acoustics
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.