Fig. 3. Regulation of the cell cycle through protein arginine methylation.

The cell cycle is mainly regulated by phase-specific oscillation of cyclin-dependent kinase (CDK)-cyclin complexes. The expression of several cyclins (Cyclin E, Cyclin D1, etc.) and CDKs is epigenetically regulated by PRMTs (not shown). CDK4 is directly methylated by PRMT1, which inhibits binding with Cyclin D and blocks cell cycle progression. In contrast, methylation of E2F1 by either PRMT1 or PRMT5 results in cell progression from G1 to S phase. Several CKIs (CDK inhibitors), such as p16, p21, and p27, are directly methylated by PRMTs to regulate their binding with CDK-cyclin complexes or their cellular localization. During mitosis, PRMT6-mediated H3R2me2a recruits Aurora B kinase into chromosomes along with CPC components, enabling H3S10 phosphorylation. Another CPC component, INCENP, is also methylated by PRMT1, which promotes its interaction with Aurora B kinase. Together, the activities of PRMT1 and PRMT6 during M phase are required for chromosome condensation and proper segregation.