G9a and G9a-Like Histone Methyltransferases and Their Effect on Cell Phenotype, Embryonic Development, and Human Disease

Abstract

Post-translational modifications of histone proteins alter the topology of the chromatin, which affect genome accessibility and thus, impact gene regulation. One type of histone modification that has a profound effect on the chromatin is methylation, where specific marking of lysine or arginine residues within the N-terminal tails of the histone core proteins control chromatin packaging and transcriptional dynamics throughout the genome. Two important histone methyltransferases are G9a and G9a-like protein-1 (GLP), whose enzymatic activities have a major influence on cell phenotype, embryonic development, cancer progression, and other human diseases. This review will provide an overview of the structural and enzymatic properties of G9a and GLP, the development of pharmacological reagents that target their catalytic activities, the impact of these enzymes on cell biology, embryogenesis, cancer progression, neurological and other human diseases. In addition, we will examine the known non-histone targets of the enzymes, to understand how G9a and GLP influence biological responses beyond their effect on histone proteins. Emphasis will be placed on highlighting the latest discoveries and examining the experimental details of several key studies that have contributed to our current understanding of the biological significance of G9a and GLP.