The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation

被引:293
作者
Montgomery, ND
Yee, D
Chen, A
Kalantry, S
Chamberlain, SJ
Otte, AP
Magnuson, T
机构
[1] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA
[4] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 SM Amsterdam, Netherlands
基金
美国国家卫生研究院;
关键词
D O I
10.1016/j.cub.2005.04.051
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PcG proteins mediate heritable transcriptional silencing by generating and recognizing covalent histone modifications. One conserved PcG complex, PRC2, is composed of several proteins including the histone methyltransferase (HMTase) Ezh2, the WD-repeat protein Eed, and the Zn-finger protein Suz12. Ezh2 methylates histone H3 on lysine 27 (H3K27) [1-4], which serves as an epigenetic mark mediating silencing. H3K27 can be mono-, di-, or trimethylated (1 mH3K27, 2mH3K27, and 3mH3K27, respectively) (5]. Hence, either PRC2 must be regulated so as to add one methyl group to certain nucleosomes but two or three to others, or distinct complexes must be responsible for 1m-, 2m-, and 3mH3K27. Consistent with the latter possibility, 2mH3K27 and 3mH3K27, but not 1mH3K27, are absent in Suz12(-/-) embryos, which lack both Suz12 and Ezh2 protein [6]. Mammalian proteins required for 1mH3K27 have not been identified. Here, we demonstrate that unlike Suz12 and Ezh2, Eed is required not only for 2m- and 3mH3K27 but also global 1mH3K27. These results provide a functionally important distinction between PRC2 complex components and implicate Eed in PRC2-independent histone methylation.
引用
收藏
页码:942 / 947
页数:6
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