Recent findings suggest that lysine and arginine-specific methylation of hi
stones may cooperate with other types of post-translational histone modific
ation to regulate chromatin structure and gene transcription. Proteins that
methylate histones on arginine residues can collaborate with other coactiv
ators to enhance the activity of specific transcriptional activators such a
s nuclear receptors, Lysine methylation of histones is associated with tran
scriptionally active nuclei, regulates other types of histone modifications
, and is necessary for proper mitotic cell divisions. The fact that some tr
anscription factors and proteins involved in RNA processing can also be met
hylated suggests that protein methylation may also contribute in other ways
to regulation of transcription and post-transcriptional steps in gene regu
lation. In future work, it will be important to develop methods for evaluat
ing the precise roles of protein methylation in the regulation of native ge
nes 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 methy
ltransferases by molecular cloning and to characterize new methyltransferas
e substrates, the regulation of methyltransferase activities, and the roles
of new methyltransferases and substrates.