Tri-methylation on K4 of histone H3 by the mixed lineage leukemia (MLL) protein leads to transcriptional activation[249] and the MLL knockdown in colon cancer cells leads to NRF2 and HO-1 down regulation further supporting the epigenetic regulation of NRF2[248]. This evidence concerns the gene NFE2L2 and malignant colon neoplasm.