Abstract
As discussed in previous chapters, the methylation of specific arginine and lysine side chains is carried out by two families of histone methyltransferases, the Protein Arginine Methyltransferase (PRMT) family for arginine, and the SET domain family for lysine. The methylation of H3K79 by Dot1 is a notable outlier. In all cases, X-ray crystallography has been a powerful technique that has provided the framework for understanding the enzyme mechanism, kinetics, regulation and specificity of these enzymes and is now a platform for the design of compounds aimed to inhibit their activity either to further understand their function or in a therapeutic setting. Notably, in combination with the structures of the complementary recognition domains that recognize their products, these structures have provided an important insight into how integral the number of methyl groups added to the acceptor amine is to making histone methylation a key process in epigenetic regulation of gene transcription. Here the concepts applied to determine their structure by X-ray crystallography are outlined, with particular emphasis on lysine methylation by the SET domain.
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Acknowledgments
This work was supported by the Worldwide Cancer Fund (AM) and by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001078), the UK Medical Research Council (FC001078), and the Wellcome Trust (FC001078).
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Wilson, J.R. (2022). Determination of Histone Methyltransferase Structure by Crystallography. In: Margueron, R., Holoch, D. (eds) Histone Methyltransferases. Methods in Molecular Biology, vol 2529. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2481-4_7
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