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.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Kouzarides, T. Cell 128, 693–705 (2007).
Rea, S. et al. Nature 406, 593–599 (2000).
Cheng, X., Collins, R.E. & Zhang, X. Annu. Rev. Biophys. Biomol. Struct. 34, 267–294 (2005).
Tachibana, M. et al. Genes Dev. 16, 1779–1791 (2002).
Xin, Z. et al. J. Biol. Chem. 278, 14996–15000 (2003).
Ikegami, K. et al. Genes Cells 12, 1–11 (2007).
Tachibana, M. et al. Genes Dev. 19, 815–826 (2005).
Collins, R.E. et al. J. Biol. Chem. 280, 5563–5570 (2005).
Patnaik, D. et al. J. Biol. Chem. 279, 53248–53258 (2004).
Tachibana, M., Sugimoto, K., Fukushima, T. & Shinkai, Y. J. Biol. Chem. 276, 25309–25317 (2001).
Rathert, P., Zhang, X., Freund, C., Cheng, X. & Jeltsch, A. Chem. Biol. 15, 5–11 (2008).
Chin, H.G. et al. Biochemistry 44, 12998–13006 (2005).
Dacwag, C.S., Ohkawa, Y., Pal, S., Sif, S. & Imbalzano, A.N. Mol. Cell. Biol. 27, 384–394 (2007).
Kirmizis, A. et al. Nature 449, 928–932 (2007).
Guccione, E. et al. Nature 449, 933–937 (2007).
Sampath, S.C. et al. Mol. Cell 27, 596–608 (2007).
Jacobs, S.A. & Khorasanizadeh, S. Science 295, 2080–2083 (2002).
Frank, R. J. Immunol. Methods 267, 13–26 (2002).
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.
About this article
Cite this article
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
Cell Communication and Signaling (2021)
Towards the understanding of the activity of G9a inhibitors: an activity landscape and molecular modeling approach
Journal of Computer-Aided Molecular Design (2020)
Monitoring the crosstalk between methylation and phosphorylation on histone peptides with host-assisted capillary electrophoresis
Analytical and Bioanalytical Chemistry (2020)
Nature Communications (2019)