Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins
2002
Kishikawa, Shotaro | Murata, Takehide | Kimura, Hiromichi | Shiota, Kunio | Yokoyama, Kazunari K
The Sp family is a family of transcription factors that bind to cisâelements in the promoter regions of various genes. Regulation of transcription by Sp proteins is based on interactions between a GCârich binding site (GGGCGG) in DNA and Câterminal zinc finger motifs in the proteins. In this study, we characterized the GCârich promoter of the gene for the DNA methyltransferase (Dnmt1) that is responsible for methylation of cytosine residues in mammals and plays a role in gene silencing. We found that a cisâelement (nucleotides −161 to −147) was essential for the expression of the mouse gene for Dnmt1. DNAâbinding assays indicated that transcription factors Sp1 and Sp3 bound to the same cisâelement in this region in a doseâdependent manner. In Drosophila SL2 cells, which lack the Sp family of transcription factors, forced expression of Sp1 or Sp3 enhanced transcription from the Dnmt1 promoter. Stimulation by Sp1 and Sp3 were independent phenomena. Furthermore, cotransfection reporter assays with a p300âexpression plasmid revealed the activation of the promoter of the Dnmt1 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 Dnmt1 gene is controled by Sp1 and Sp3 and that p300 is involved in the activation by Sp3.
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