Previous studies had found SETD1A maintained the WNT pathway activation by stabilizing β-catenin,44 and H3K4 trimethylation induced by demethylase inhibitor blocked the TGF-β-induced invasion and migration of cancer cells, suggesting H3K4me3 modification was one of the essential epistatic regulators of the two cancer driver pathways.45 Our study supplemented that the non-catalytic composition of histone modification enzymes could reshape the histone mark signature of the genome. The gene discussed is SETD1A; the disease is cancer.