Transcriptional regulation on DNMT gene expression. (A) p53 transcriptionally suppresses DNMTs through binding with Sp1 protein to the DNMT1, 3A and 3B promoters. (B) RB transcriptionally suppresses DNMT1/3A through binding with E2F1 protein to the DNMT1 and 3A promoters. (C) FOXO3a binds to the FOXO3a DNA element of the DNMT3B promoter to repress DNMT3B transcription. (D) Clinically, overexpressed MDM2 dramatically induces DNMT1, DNMT3A, and DNMT3B expression by negative control over p53, RB and FOXO3a leading to methylation of multiple TSGs and tumorigenesis.