Interestingly, this observation also holds for models with genetic mutations of epigenetic regulators that have been associated with widespread CGI hypermethylation in human cancer, such as Tet2 and Idh1, which more recent reports suggest may also be acting to control cell state identity through alternative mechanisms such as enhancer activity or nuclear topology (Fig. 6a–c, Additional file 2: Fig. S7a-f) [52–54]. The gene discussed is TET2; the disease is cancer.