B cell-specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5

被引:91
作者
Johnson, K
Pflugh, DL
Yu, DN
Hesslein, DGT
Lin, KI
Bothwell, ALM
Thomas-Tikhonenko, A
Schatz, DG
Calame, K
机构
[1] Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA
[2] Yale Univ Med, Immunobiol Sect, New Haven, CT 06520 USA
[3] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA
[4] Yale Univ Med, Dept Cell Biol, New Haven, CT 06520 USA
[5] Yale Univ Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
[6] Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA
关键词
D O I
10.1038/ni1099
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunoglobulin heavy chain rearrangement (V-H-to-DJ(H)) occurs only in B cells, suggesting it is inhibited in other lineages. Here we found that in the mouse V-H locus, methylation of lysine 9 on histone H3 (H3-K9), a mark of inactive chromatin, was present in non-B lineage cells but was absent in B cells. As others have shown that H3-K9 methylation can inhibit V(D)J recombination on engineered substrates, our data support the idea that H3-K9 methylation inhibits endogenous V-H-to-DJ(H) recombination. We also show that Pax5, a transcription factor required for B cell commitment, is necessary and sufficient for the removal of H3-K9 methylation in the V-H locus and provide evidence that one function of Pax5 is to remove this inhibitory modification by a mechanism of histone exchange, thus allowing B cell-specific V-H-to-DJ(H) recombination.
引用
收藏
页码:853 / 861
页数:9
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