Mixed Lineage Leukemia (MLL1) plays a major role in epigenetic regulation through methylation of histone 3 at lysine 4 (H3K4) to activate gene transcription. Methylation of H3K4 leads to upregulation of developmental genes, including HOX family members. In addition to its methylation activity, MLL1 has been shown to co-localize with Pol II at several genomic elements. Consequently, MLL1 has very low basal methyltransferase activity unless complexed with the activating protein complex of WDR5, Ash2L, and RbBP5 (MLL/WAR complex). This C-terminal fragment of MLL1, residues 3762 - 3969, contains the SET1 domain for methyltransferase activity, and the WIN motif for binding the WAR complex. The protein DPY-30 has also been reported to associate with the MLL1-WAR complex. MLL1 is also available as a component of the MLL1/WAR complex and MLL1/WARD complex .
