Chapter 16 - Enzymatic Assays of Histone Methyltransferase Enzymes

Abstract

Protein methyltransferases are essential for epigenetic regulation of gene expression through methylation of histones and non-histone proteins such as transcription factors, and have been implicated to play key roles in human diseases including cancer. Therefore, they are widely recognized as potential targets for the treatment of human diseases, that is, by specifically modulating the methyltransferase activities. Yet our understanding of the complex regulation of protein lysine (K) or arginine (R) methyltransferases is largely limited by the lack of potent and selective chemical probes to perturb, especially in vivo, the activities of specific enzymes. To overcome this hurdle, a number of enzymatic assays have been developed to measure the activities of various protein methyltransferases and some have been applied to high-throughput screening for identification of chemical modulators. Herein, we discuss several properties of protein K/R methyltransferases and focus on the achievements and progress in the development and application of enzymatic assays to characterize protein methyltransferase activities.