A novel regulatory element in the dnmt1 gene that responds to co-activation by Rb and c-Jun.
Rb, c-Jun and dnmt1 play critical roles in the process of cellular differentiation. We demonstrate that a regulatory region of murine dnmt1 contains an element which is responsible for transactivation by Rb and c-Jun in P19 embryocarcinoma cells which is not observed in Y1 adrenocarcinoma cells. During differentiation of P19 cells, the induction of Rb and c-Jun coincides with an increase of dnmt1 mRNA. Using linker scanning mutagenesis we identify the element that is responsible for this activation to be a non-canonical AP-1 site. Our data is an example of how a proto-oncogene activates its downstream effectors by recruiting a tumor suppressor. This interaction of Rb and a proto-oncogene might play an important role in differentiation. The responsiveness of dnmt1 to this type of signal is consistent with an important role for regulated expression of dnmt1 during cellular differentiation.
Slack
A
A
Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal, Canada.
Pinard
M
M
Araujo
F D
FD
Szyf
M
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D002457:Cell Extracts; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D002457:Cell Extracts; D016755:Proto-Oncogene Proteins c-jun; D016160:Retinoblastoma Protein; D018808:Transcription Factor AP-1; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse