The biological functions of lysine methyltransferase PR-SET7

PR-SET7 (also named SET8 or KMT5a) is a sole lysine methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20me1) in higher eukaryotes.The abundance of PR-SET7 is dynamically mediated by the distinct E3 ubiquitin ligases in different cell cycle phases.PR-SET7 is closely related to the regulation of cell proliferation, and the H4K20me1 catalyzed by PR-SET7 has been implicated in regulating the diverse biological processes, including DNA replication, chromosome condensation and the activation of DNA replication checkpoints.Loss of PR-SET7 results in massive DNA damage, cell cycle arrest and induction of apoptosis.In addition, PR-SET7 involves in regulating the transcription of several genes, such as ERα, Wnt and p53.PR-SET7 is also essential for individual development and participates in the formation of genomic imprinting.Moreover, PR-SET7 has been reported to promote tumorigenesis and metastasis, suggesting that PR-SET7 may be a potential target for cancer treatment.In this review, we focus on analyzing the structure of PR-SET7 and factors influencing histone modification on regulation of PR-SET7, and discuss the mechanisms by which PR-SET7 modulates cell-cycle progression, gene transcription, individual development and tumorigenesis.