Role of protein methylation in chromatin remodeling and transcriptional regulation.

Recent findings suggest that lysine and arginine-specific methylation of histones may cooperate with other types of post-translational histone modification to regulate chromatin structure and gene transcription. Proteins that methylate histones on arginine residues can collaborate with other coactivators to enhance the activity of specific transcriptional activators such as nuclear receptors. Lysine methylation of histones is associated with transcriptionally active nuclei, regulates other types of histone modifications, and is necessary for proper mitotic cell divisions. The fact that some transcription factors and proteins involved in RNA processing can also be methylated suggests that protein methylation may also contribute in other ways to regulation of transcription and post-transcriptional steps in gene regulation. In future work, it will be important to develop methods for evaluating the precise roles of protein methylation in the regulation of native genes in physiological settings, e.g. by using chromatin immunoprecipitation assays, differentiating cell culture systems, and genetically altered cells and animals. It will also be important to isolate additional protein methyltransferases by molecular cloning and to characterize new methyltransferase substrates, the regulation of methyltransferase activities, and the roles of new methyltransferases and substrates.