Histone-lysine N-methyltransferase SETD8 (SETD8) (SETD8)

Histone-lysine N-methyltransferase SETD8 (SETD8), also known as PR-Set7 or KMT5A, is the exclusive enzyme responsible for the monomethylation of histone H4 at lysine 20 (H4K20me1) [UniProt: Q9NQR1]. This specific epigenetic modification is crucial for maintaining genomic stability, regulating the timing of DNA replication, and facilitating the DNA damage response [PubMed: 21907244]. SETD8 protein levels fluctuate during the cell cycle, being actively degraded during S phase and peaking in G2/M to ensure proper chromatin organization [PubMed: 21454524]. Dysregulation and overexpression of SETD8 have been implicated in various cancers, including breast, lung, and liver carcinomas, where it promotes tumor cell proliferation, survival, and epithelial-mesenchymal transition [PubMed: 27535395]. As a result, SETD8 has become an attractive target for small-molecule inhibition, with compounds like UNC0379 demonstrating the potential to disrupt its oncogenic functions in preclinical models [PubMed: 24905302].

Other names

PR-Set7SET8KMT5ALysine N-methyltransferase 5ASET domain-containing protein 8H4-K20-HMTase SETD8

Inhibition of the lysine methyltransferase activity of SETD8, specifically preventing the monomethylation of histone H4 at lysine 20 (H4K20me1).