Histone-lysine N-methyltransferase PRDM9 (PRDM9)

PRDM9 (Histone-lysine N-methyltransferase PRDM9) is a meiosis-specific histone methyltransferase that controls activation of meiotic recombination hotspots by catalyzing mono-, di-, and trimethylation of histone H3 at lysine 4 (H3K4) and lysine 36 (H3K36)[1][2][5][6]. It contains a PR/SET catalytic domain responsible for methyltransferase activity, a KRAB domain (for protein-protein interactions), and a C-terminal zinc finger array that binds specific DNA sequences at recombination hotspots[2][3][4][5]. PRDM9’s methyltransferase activity regulates local chromatin state, creating nucleosome-depleted regions that enable double-strand breaks required for homologous recombination in meiosis[3][4][6]. Loss or mutation of PRDM9 in mammals leads to infertility, confirming its essential role in germ cell development and fertility[1][2]. No drugs currently target PRDM9 clinically, but its role in meiosis makes it a focus in reproductive biology and a potential risk for off-target effects regarding fertility if modulated therapeutically.

Other names

PR/SET domain 9PR domain-containing protein 9MeisetzKMT8BZNF899PFM6PR domain zinc finger protein 9Protein-lysine N-methyltransferase PRDM9[histone H3]-lysine36 N-trimethyltransferase PRDM9[histone H3]-lysine4 N-trimethyltransferase PRDM9[histone H3]-lysine9 N-trimethyltransferase PRDM9[histone H4]-lysine20 N-methyltransferase PRDM9histone methyl transferaseminisatellite binding protein 3 (115kD)MSBP3

Small molecules targeting the SET domain would act by inhibiting H3K4 and H3K36 methyltransferase activity (inhibition of lysine methylation) No clinical drugs known to target PRDM9 directly as of this writing