POU5F1 and cancer: In this study, we identified multiple methylated lysine and arginine residues in OCT4 proteins in the cellular contexts of PSCs and somatic cancer cells, and demonstrated that LSD1 can maintain the un-methylated status of the crucial OCT4-K222 residue to prevent the ‘locked-in’ mode engagement of the OCT4 PORE-homodimers and thereby allowing for the transcription of the PORE genes.