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 differen tiation. We demonstrate that a regulatory region of murine dnmt1 contains a n element which is responsible for transactivation by Rb and c-Jun in P19 e mbryocarcinoma cells which is not observed in Y1 adrenocarcinoma cells. Dur ing differentiation of P19 cells, the induction of Rb and c-Jun coincides w ith an increase of dnmt1 mRNA. Using linker scanning mutagenesis we identif y 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 do wnstream effecters by recruiting a tumor suppressor. This interaction of Rb and a protooncogene might play an important role in differentiation. The r esponsiveness of dnmt1 to this type of signal is consistent with an importa nt role for regulated expression of dnmt1 during cellular differentiation. (C) 2001 Published by Elsevier Science B.V. All rights reserved.