SETD1A is a component of the SET1 histone methyltransferase (HMT) complex. This complex specifically methylates lysine 4 of histone H3, but only if the neighboring lysine 9 residue is not yet methylated. Methylation of H3K4 represents a specific tag for epigenetic transcriptional activation. SETD1A shows a non-overlapping localization with SETD1B, suggesting that both proteins play a specific role in the epigenetic control of chromatin structure and gene expression.