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 (Dnmt1) 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 Dnmt1. 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 Dnmt1 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 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.
Kishikawa
Shotaro
S
Gene Engineering Division, Department of Biological Systems, BioResource Center, RIKEN (The Institute of Physical & Chemical Research), Japan.
Murata
Takehide
T
Kimura
Hiromichi
H
Shiota
Kunio
K
Yokoyama
Kazunari K
KK
D016475:3T3 Cells; D000225:Adenine / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D050881:E1A-Associated p300 Protein; D005809:Genes, Regulator / Q000235:genetics*; D006151:Guanosine / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D051705:Sp3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D016335:Zinc Fingers / Q000502:physiology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D006151:Guanosine; D051705:Sp3 Transcription Factor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D000225:Adenine