Dysregulation of specific histone-modifying enzymes such as histone acetyltransferases, histone deacetylases (HDACs), histone demethylases or their catalytic subunits (e.g., EZH2), through overexpression and loss-of-function mutations in the encoding genes (KDM6A, HDAC1, HDAC2, HDAC3, EZH2, MLL2 [KMT2D], SETD2), plays role in cancer initiation, increased genomic instability and aggressiveness, stemness, progression, and metastasis (26, 35, 38). The gene discussed is EZH2; the disease is cancer.