title: YY1 controls Igκ repertoire and B-cell development, and localizes with condensin on the Igκ locus.
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.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Pan
authors.forename: Madhusudhan
authors.initials: M
authors.lastname: Papasani
authors.forename: Yi
authors.initials: Y
authors.lastname: Hao
authors.forename: Marco
authors.initials: M
authors.lastname: Calamito
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.forename: William J
authors.initials: WJ
authors.lastname: Quinn Iii
authors.forename: Arindam
authors.initials: A
authors.lastname: Basu
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.forename: Suchita
authors.initials: S
authors.lastname: Hodawadekar
authors.forename: Kristina
authors.initials: K
authors.lastname: Zaprazna
authors.forename: Huifei
authors.initials: H
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: David
authors.initials: D
authors.lastname: Allman
authors.forename: Michael
authors.initials: M
authors.lastname: Cancro
authors.forename: Michael L
authors.initials: ML
authors.lastname: Atchison
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D055785:Gene Knockdown Techniques; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D017384:Sequence Deletion; D014161:Transduction, Genetic; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D046912:Multiprotein Complexes; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; C108312:condensin complexes; D004247:DNA; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2; D000251:Adenosine Triphosphatases