This is well established in many types of cancer, as: (1) CSC markers are directly regulated by epigenetic modifications (i.e., CD133 and DCLK1) (Yi et al., 2008; Vedeld et al., 2014); (2) CSCs exhibit mutations in chromatin remodeler components (loss of function mutations of PRC2 complex and deregulation of EZH2) (van Vlerken et al., 2013); (3) EMT, which confers cells with tumor-initiating capabilities and CSC properties (Mani et al., 2008), is finely controlled by epigenetic mechanisms (Kanwar et al., 2010; Beck et al., 2015; Avgustinova and Benitah, 2016). The gene discussed is EZH2; the disease is cancer.