Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins

The Sp family is a family of transcription factors that bind to cis -elements in the promoter regions of various genes. Regulation of transcription by Sp proteins is based on interactions between a GC-rich binding site (GGGCGG) in DNA and C-terminal zinc finger motifs in the proteins. In this study, we characterized the GC-rich promoter of the gene for the DNA methyltransferase (Dnmt 1) that is responsible for methylation of cytosine residues in mammals and plays a role in gene silencing. We found that a cis -element (nucleotides -161 to -147) was essential for the expression of the mouse gene for Dnmt 1. DNA-binding assays indicated that transcription factors Sp1 and Sp3 bound to the same cis -element in this region in a dose-dependent manner. In Drosophila SL2 cells, which lack the Sp family of transcription factors, forced expression of Sp1 or Sp3 enhanced transcription from the Dnmt 1 promoter. Stimulation by Sp1 and Sp3 were independent phenomena. Furthermore, cotransfection reporter assays with a p300-expression plasmid revealed the activation of the promoter of the Dnmt 1 gene in the presence of Sp3. The transcriptional coactivator p300 interacted with Sp3 in vivo and in vitro . Our results indicate that expression of the Dnmt 1 gene is controled by Sp1 and Sp3 and that p300 is involved in the activation by Sp3.