Yin Yang 1 is a critical regulator of B-cell development

被引:193
作者
Liu, Huifei
Schmidt-Supprian, Marc
Shi, Yujiang
Hobeika, Elias
Barteneva, Natasha
Jumaa, Hassan
Pelanda, Roberta
Reth, Michael
Skok, Jane
Rajewsky, Klaus
Shi, Yang
机构
[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[2] CBR Inst Biomed Res Inc, Boston, MA 02115 USA
[3] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany
[4] Univ Freiburg, Inst Biol 3, D-79108 Freiburg, Germany
[5] CBR Inst Biomed Res Inc, Flow Cytometry Core Facil, Boston, MA 02115 USA
[6] UCL, Div Infect & Immun, Dept Immunol & Mol Pathol, London W1T 4JF, England
基金
英国惠康基金;
关键词
YY1; immunoglobulin gene; B-cell development; V(D)J recombination;
D O I
10.1101/gad.1529307
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The role of the transcription factor Yin Yang 1 (YY1) in development is largely unknown. Here we show that specific ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and a block in the progenitor-B-to-precursor-B-cell transition, which was partially rescued by a prerearranged IgH transgene. Three-dimensional DNA fluorescence in situ hybridization analysis revealed an important function for YY1 in IgH locus contraction, a process indispensable for distal V-H to D(H)J(H) recombination. We provide evidence that YY1 binds the intronic Ei mu enhancer within the IgH locus, consistent with a direct role for YY1 in V(H)D(H)J(H) recombination. These findings identified YY1 as a critical regulator of early B-cell development.
引用
收藏
页码:1179 / 1189
页数:11
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