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Epigenetic Therapy of Cancer pp 189–226Cite as

Histone Methyltransferases: Opportunities in Cancer Drug Discovery

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Abstract

The potential for developing therapeutics for cancers driven by aberrant gene expression is becoming a reality in recent years, largely due to the identification and characterization of the enzymatic components regulating chromatin structure and function. One of the major classes of chromatin-modifying enzymes is the histone methyltransferases. These enzymes catalyze the methylation of lysine and arginine residues on the core nucleosomal histones. The methylation pattern present on the histones is associated with different chromatin states depending upon the particular site of methylation. The lysine and arginine methyltransferases (KMTs and RMTs) comprise enzyme families with promising therapeutic potential because they have been found to be altered in diseases with high unmet need (e.g., cancer) and are amenable to small molecule drug discovery efforts (Copeland et al., Nat Rev Drug Discov 8(9):724–732, 2009). The purpose of this chapter is to review the histone lysine and arginine methyltransferases with particular focus on their histone substrates and their association with cancer and status of the development of small molecule inhibitors.

Richard Chesworth and Tim J. Wigle contributed equally to the chapter.

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Acknowledgement

We thank Dr. Robert A. Copeland for helpful discussions and careful reading of the Chapter.

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Authors and Affiliations

  1. Department of Molecular Discovery, 400 Technology Square 4th floor, Cambridge, MA, 02139, USA

    Richard Chesworth, Tim J. Wigle & Kevin W. Kuntz

  2. Department of Biology, 400 Technology Square 4th floor, Cambridge, MA, 02139, USA

    Jesse J. Smith & Victoria M. Richon

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  1. Richard Chesworth
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  2. Tim J. Wigle
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Correspondence to Victoria M. Richon .

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  1. Department of Hematology/Oncology, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany

    Michael Lübbert

  2. Norris Comprehensive Cancer Center Urologic Cancer Res. Lab., University of Southern California Dept. Biochemistry & Molecular Biology, Los Angeles, California, USA

    Peter A. Jones

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Chesworth, R., Wigle, T.J., Kuntz, K.W., Smith, J.J., Richon, V.M. (2014). Histone Methyltransferases: Opportunities in Cancer Drug Discovery. In: Lübbert, M., Jones, P. (eds) Epigenetic Therapy of Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38404-2_9

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