Histone modifications associated with somatic hypermutation

被引:59
作者
Odegard, VH
Kim, ST
Anderson, SM
Shlomchik, MJ
Schatz, DG
机构
[1] Yale Univ, Immunol Sect, Sch Med, New Haven, CT 06520 USA
[2] Yale Univ, Howard Hughes Med Inst, Sch Med, New Haven, CT 06520 USA
关键词
D O I
10.1016/j.immuni.2005.05.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A number of modified histones, including acetylated H3 and H4 and phosphorylated H2AX (gamma H2AX), are associated with V(D)J recombination and class switch recombination (CSR). In contrast, little is known concerning the chromatin modifications associated with somatic hypermutation (SHM) in vivo. Here, we report that several modifications-including histone acetylation and H3-lysine 4 methylation-fail to demarcate an actively hypermutating immunoglobulin (Ig) locus or to correlate spatially with SHM within Ig loci. Furthermore, no obvious association between SHM and gamma H2AX could be detected. Instead, we find that the phosphorylated form of histone H2B (H2B(Ser14P)) correlates tightly with SHM and CSR. Phosphorylation of H2B within Ig variable and switch regions requires AID and may be mediated by the histone kinase Mst1. These findings indicate that SHM and CSR trigger distinct DNA damage responses and identify a novel histone modification pattern for SHM consisting of H2B(Ser14P) in the absence of gamma H2AX.
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页码:101 / 110
页数:10
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