Histone methyltransferase complexes in transcription, development, and cancer

Dynamic regulation of the mammalian epigenome enables precise control of the developmental gene expression programs that direct stem and progenitor cell proliferation, self-renewal, and differentiation. Among the posttranslational modifications that occur on chromatin, histone methylation is a key epigenetic mark with central roles in virtually all DNA-templated processes, including gene transcription by RNA polymerase II (RNAPII). Histone methylation is catalyzed by various histone methyltransferase enzymes, which typically operate within the context of conserved macromolecular complexes. Characterization of the composition and function of histone methyltransferase complexes is critical to understanding the molecular and epigenetic underpinning of cell fate decisions during development. Aberrant histone methylation is frequently observed at the onset and progression of the disease state, originating either directly by inactivating or activating causal mutations that drive pathogenesis or indirectly as facilitators that perpetuate cancer-related pathways. Here, we review the molecular biology of diverse, often conserved, multicomponent histone methyltransferase complexes with emphasis on the biochemical and physiological roles of these complexes in transcription regulation and chromatin architecture in normal development and human diseases such as cancer.