Transcription profiling of mouse embryonic fibroblasts deleted for G9a reconstituted with empty vector (delta), wild type FLAG-G9a (WT), FLAG-G9a K165A (K165A) or FLAG-G9a H1093K catalytic mutant reveasl methylation of hMTase G9a on a histone-like site regulates protein complex assembly
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ABSTRACT: Gene expression in eukaryotes is tightly linked to the methylation state of specific lysine residues within the N-terminal region of the core histone proteins. While the mechanisms connecting histone lysine methylation to effector protein recruitment and control of gene activity are increasingly well understood, it remains unknown whether non-histone chromatin proteins are targets for similar modification-recognition systems. Here we show that histone H3 and the H3 methyltransferase G9a share a conserved methylation motif that is both necessary and sufficient to mediate in vivo interaction with the potent epigenetic regulator Heterochromatin Protein 1 (HP1). As with H3, G9a-HP1 interaction is dependent on lysine methylation and can be reversed by adjacent phosphorylation. NMR analysis demonstrates that the HP1 chromodomain recognizes methyl-G9a through a binding mode similar to that used in recognition of methyl-H3, and that adjacent phosphorylation directly antagonizes G9a-HP1 interaction. In addition to uncovering the chromodomain as a generalized methyl-lysine binding module, these data identify histone-like modification cassettes (or âhistone mimicsâ) as an entirely new class of non-histone methylation targets, and directly demonstrate the relevance of the principles underlying the histone code to the regulation of non-histone proteins. Experiment Overall Design: Two independent Affymetrix gene expression microarray analyses were performed on samples from G9a-deleted MEFs reconstituted with empty vector (delta), wild type FLAG-G9a (WT), FLAG-G9a K165A (K165A) or FLAG-G9a H1093K catalytic mutant (H1093K).
ORGANISM(S): Mus musculus
SUBMITTER: Agnes Viale
PROVIDER: E-GEOD-8011 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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