Methylation of a Histone Mimic within the Histone Methyltransferase G9a Regulates Protein Complex Assembly
| Autor: | Srihari C. Sampath, Alexander Tarakhovsky, Agnes Viale, Ming-Ming Zhou, Ingrid Mecklenbräuker, Eugene Rudensky, Ivan Marazzi, Andrew N. Krutchinsky, Brian T. Chait, Srinath C Sampath, Kyoko L. Yap |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Chromosomal Proteins Non-Histone Histone lysine methylation Molecular Sequence Data Biology Cell Line Histones Mice 03 medical and health sciences Histone H1 Histone methylation Histone H2A Animals Humans Histone code Amino Acid Sequence Protein Methyltransferases Histone octamer Phosphorylation Molecular Biology 030304 developmental biology 0303 health sciences Binding Sites Lysine Molecular Mimicry 030302 biochemistry & molecular biology EZH2 Histone-Lysine N-Methyltransferase Cell Biology DNA Methylation Gene Expression Regulation Biochemistry Chromobox Protein Homolog 5 Multiprotein Complexes Histone methyltransferase Histone Methyltransferases Protein Binding |
| Zdroj: | Molecular Cell. 27(4):596-608 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2007.06.026 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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