Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly

被引:196
作者
Sampath, Srihari C.
Marazzi, Ivan
Yap, Kyoko L.
Sampath, Srinath C.
Krutchinsky, Andrew N.
Mecklenbraeuker, Ingrid
Viale, Agnes
Rudensky, Eugene
Zhou, Ming-Ming
Chait, Brian T.
Tarakhovsky, Alexander
机构
[1] Rockefeller Univ, Lab Lymphocyte Signaling, New York, NY 10021 USA
[2] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10021 USA
[3] Mt Sinai Sch Med, Dept Physiol & Mol Biophys, New York, NY 10029 USA
[4] Mem Sloan Kettering Canc Ctr, Dept Biol Mol, Genom Core Lab, New York, NY 10021 USA
关键词
D O I
10.1016/j.molcel.2007.06.026
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
Epigenetic gene silencing in eukaryotes is regulated in part by lysine methylation of the core histone proteins. While histone lysine methylation is known to control gene expression through the recruitment of modification-specific effector proteins, it remains unknown whether nonhistone chromatin proteins are targets for similar modification-recognition systems. Here we show that the histone H3 methyltransferase G9a. contains a conserved methylation motif with marked sequence similarity to H3 itself. As with methylation of H3 lysine 9, autocatalytic G9a methylation is necessary and sufficient to mediate in vivo interaction with the epigenetic regulator heterochromatin protein 1 (HP1), and this methyl-dependent interaction can be reversed by adjacent G9a phosphorylation. NMR analysis indicates that the HP1 chromodomain recognizes methyl-G9a through a binding mode similar to that used in recognition of methyl-H3K9, demonstrating that the chromodomain functions as a generalized methyl-lysine binding module. These data reveal histone-like modification cassettes-or "histone mimics"-as a distinct class of nonhistone methylation targets and directly extend the principles of the histone code to the regulation of nonhistone proteins.
引用
收藏
页码:596 / 608
页数:13
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