SET7/9 also known as SETD7 is a histone methyltransferase that plays a crucial role in gene expression regulation through methylating lysine 4 on histone H3, a modification essential for transcription activation. This methylation event is vital for chromatin remodeling and influences transcriptional machinery recruitment, impacting cellular processes such as differentiation and development. SET7/9 operates through a complex mechanism involving S-adenosyl-L-methionine, recognizing specific lysine residues in histones to ensure precise gene expression regulation. Unique structural features of SET7/9, including binding pocket and substrate-specific channel, allow selective interaction with unmethylated lysine residues, underscoring SET7/9′s importance in epigenetic regulation and cellular function.