Control elements of Dnmt1 gene are regulated in cell-cycle dependent manner.

The Dnmt1 gene is constitutively expressed and is required for the maintenance of global methylation after DNA replication. We investigated here the effects of histone deacetylase (HDAC) inhibitor and DNA demetylation agent on promoter activity of mouse Dnmt1 gene in somatic cells. The promoter activity of Dnmt1 gene was increased approximately 2-fold in the treatment of cells by Tricostatin A (TSA) at 1 x 10(-8) M, as compared with that without treatment of TSA. By contrast, treatment with 5-azacytidne (5aza-C) did not affect the promoter activity of the Dnmt1 gene. This result indicates the Dnmt1 gene is possibly regulated by histone acetylation. We also examined the expression levels of Dnmt1 gene and of its control elements like Sp1, Sp3 and p300 by the chromatin immunoprecipitation and Western blot analysis. The expression of Dnmt1 gene is observed at early S phase. Sp1 is recruited mainly at the G1 phase and Sp3 is recruited at the early S phase. p300 is also obviously recruited at the second S phase. These data indicated that the regulators of Dnmt1 gene were controlled in cell-cycle dependent manner.