By methylation of peptide arrays, we determined the specificity profile of the protein methyltransferase G9a. We show that it mostly recognizes an Arg-Lys sequence and that its activity is inhibited by methylation of the arginine residue. Using the specificity profile, we identified new non-histone protein targets of G9a, including CDYL1, WIZ, ACINUS and G9a (automethylation), as well as peptides derived from CSB. We demonstrate potential downstream signaling pathways for methylation of non-histone proteins.
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The US National Institutes of Health (GM068680) and the Bundesministerium für Bildung und Forschung Biofuture program have supported this work. We thank M.T. Bedford (University of Texas M.D. Anderson Cancer Center) for the GST-HP1β expression construct and M. Yoshida (RIKEN) for technical advice on anti-pan methyllysine antibodies. Technical assistance by M. Schwerdtfeger (Jacobs University Bremen) is gratefully acknowledged.
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Rathert, P., Dhayalan, A., Murakami, M. et al. Protein lysine methyltransferase G9a acts on non-histone targets. Nat Chem Biol 4, 344–346 (2008). https://doi.org/10.1038/nchembio.88
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