Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly Journal Article
| Authors: | Sampath, S. C.; Marazzi, I.; Yap, K. L.; Krutchinsky, A. N.; Mecklenbräuker, I.; Viale, A.; Rudensky, E.; Zhou, M. M.; Chait, B. T.; Tarakhovsky, A. |
| Article Title: | Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly |
| Abstract: | 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. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; protein phosphorylation; nonhuman; binding affinity; protein domain; proteins; mouse; animals; chromosomal proteins, non-histone; mice; cell line; protein binding; protein interaction; phosphorylation; dna methylation; gene expression regulation; dna; amino acid sequence; molecular sequence data; eukaryota; epigenetics; histone; histone methyltransferase; histone-lysine n-methyltransferase; histone h3; models, molecular; multiprotein complexes; binding sites; catalysis; histones; nuclear magnetic resonance; lysine; protein methylation; heterochromatin protein 1; molecular mimicry |
| Journal Title: | Molecular Cell |
| Volume: | 27 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2007-08-17 |
| Start Page: | 596 |
| End Page: | 608 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2007.06.026 |
| PUBMED: | 17707231 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 57" - "Export Date: 17 November 2011" - "CODEN: MOCEF" - "Source: Scopus" |
