The RB protein can repress gene transcription by directly binding to the transactivation domain of E2F in a complex on the promoters of the E2F target genes including DNMT3A. 13 Accordingly, RB is involved in transcriptional regulation of DNMT3A gene in cancer cells,13 however, the detailed role of the RB-DNMT3A pathway remains to be fully elucidated. The gene discussed is DNMT3A; the disease is cancer.