TAILIEUCHUNG - Báo cáo Y học: 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. | Eur. J. Biochem. 269 2961-2970 2002 FEBS 2002 doi Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins Shotaro Kishikawa1 2 Takehide Murata1 Hiromichi Kimura2 Kunio Shiota2 and Kazunari K. Yokoyama1 1Gene Engineering Division Department of Biological Systems BioResource Center RIKEN The Institute of Physical Chemical Research Japan department of Animal Resource Science Veterinary Medical Sciences The University of Tokyo Japan 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 add C-lermiaal icc iigger motifs in the proteins. In this study we characterized the GC-rich promoter of the gene for the DNA methyltransferase Dnmt1 that IS repomsibk for methykliion of cytosine residues in mammals and plays a role in gene silencing. We found that a cis-element nucleotides -161 to -147 wss essnntial for hie expresóon o t hie mosise gene for Dnmt1. DNA-binding assays indicated that transcription factors Sp1 and Sp3 bound to the same ciselement 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. Keywords Dnmt1 gene activation of transcription Sp1 Sp3 p300. Transcription is regulated by the combinational actions of proteins that bind to distinct promoter and enhancer elements. In .

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