CHAPTER 11. Histone Methyltransferase Activity Assays

Histone methyltransferases (HMTs) methylate either the lysine or arginine residues on histones and other proteins and play a crucial role in epigenetic regulation. Over 70 HMTs are encoded by the human genome, and many have been implicated in the aetiology of cancer, inflammatory diseases, neurodegenerative diseases and other conditions. There are currently about a dozen HMT activity assays available, and many of these assay formats are applicable to other epigenetic factors, such as histone acetyltransferases, histone deacetylases, and histone and DNA demethylases. Many factors need to be considered in selecting an HMT assay for drug discovery studies, including cost, adaptability to high-throughput screening, and rates of false positives and false negatives. This chapter describes the mechanisms of the major assay platforms available for HMT screening and profiling and presents the advantages and limitations associated with each.