YY1 controls Ig[kappa] repertoire and B-cell development, and localizes with condensin on the Ig[kappa] 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 necess...
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creator | Pan, Xuan Papasani, Madhusudhan Hao, Yi Calamito, Marco Wei, Fang Quinn Iii, William J Basu, Arindam Wang, Junwen Hodawadekar, Suchita Zaprazna, Kristina Liu, Huifei Shi, Yang Allman, David Cancro, Michael Atchison, Michael L |
description | 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. [PUBLICATION ABSTRACT] |
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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. [PUBLICATION ABSTRACT]</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2013.66</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Heidelberg: Blackwell Publishing Ltd</publisher><subject>Amino acids ; Bone marrow ; Genomics ; Immunoglobulins ; Molecular biology ; Proteins</subject><ispartof>The EMBO journal, 2013-04, Vol.32 (8), p.1168</ispartof><rights>Copyright Nature Publishing Group Apr 17, 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Pan, Xuan</creatorcontrib><creatorcontrib>Papasani, Madhusudhan</creatorcontrib><creatorcontrib>Hao, Yi</creatorcontrib><creatorcontrib>Calamito, Marco</creatorcontrib><creatorcontrib>Wei, Fang</creatorcontrib><creatorcontrib>Quinn Iii, William J</creatorcontrib><creatorcontrib>Basu, Arindam</creatorcontrib><creatorcontrib>Wang, Junwen</creatorcontrib><creatorcontrib>Hodawadekar, Suchita</creatorcontrib><creatorcontrib>Zaprazna, Kristina</creatorcontrib><creatorcontrib>Liu, Huifei</creatorcontrib><creatorcontrib>Shi, Yang</creatorcontrib><creatorcontrib>Allman, David</creatorcontrib><creatorcontrib>Cancro, Michael</creatorcontrib><creatorcontrib>Atchison, Michael L</creatorcontrib><title>YY1 controls Ig[kappa] repertoire and B-cell development, and localizes with condensin on the Ig[kappa] locus</title><title>The EMBO journal</title><description>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. [PUBLICATION ABSTRACT]</description><subject>Amino acids</subject><subject>Bone marrow</subject><subject>Genomics</subject><subject>Immunoglobulins</subject><subject>Molecular 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Junwen</au><au>Hodawadekar, Suchita</au><au>Zaprazna, Kristina</au><au>Liu, Huifei</au><au>Shi, Yang</au><au>Allman, David</au><au>Cancro, Michael</au><au>Atchison, Michael L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>YY1 controls Ig[kappa] repertoire and B-cell development, and localizes with condensin on the Ig[kappa] locus</atitle><jtitle>The EMBO journal</jtitle><date>2013-04-17</date><risdate>2013</risdate><volume>32</volume><issue>8</issue><spage>1168</spage><pages>1168-</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><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. [PUBLICATION ABSTRACT]</abstract><cop>Heidelberg</cop><pub>Blackwell Publishing Ltd</pub><doi>10.1038/emboj.2013.66</doi></addata></record> |
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subjects | Amino acids Bone marrow Genomics Immunoglobulins Molecular biology Proteins |
title | YY1 controls Ig[kappa] repertoire and B-cell development, and localizes with condensin on the Ig[kappa] locus |
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