Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins
Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins
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DOI：
10.1046/j.1432-1033.2002.02972.x
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发表时间：
2002-06-01
期刊：
影响因子：
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通讯作者：
Yokoyama, KK
中科院分区：
文献类型：
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作者：
Kishikawa, S;Murata, T;Yokoyama, KK
Sp家族是一个转录因子家族，与不同基因启动子区域的顺式元件结合。Sp蛋白对转录的调控是基于DNA中富含GC的结合位点(GGGCGG)与蛋白质中C端锌指基序之间的相互作用。在这项研究中，我们鉴定了富含GC的DNA甲基转移酶(DNMT1)基因的启动子，该基因负责哺乳动物胞嘧啶残基的甲基化，并在基因沉默中发挥作用。DNA结合分析表明，转录因子Sp1和Sp3以剂量依赖的方式与该区域的同一顺式元件结合。在缺乏Sp转录因子家族的果蝇SL2细胞中，Sp1或Sp3的强制表达促进了Dnmt1启动子的转录。Sp1和Sp3的刺激是独立的现象。此外，与p300表达载体的共转染报告显示，在SP3存在的情况下，DNMT1基因的启动子被激活。转录辅活化子p300在体内和体外与SP3相互作用。我们的结果表明，DNMT1基因的表达受Sp1和Sp3的调控，而p300参与了Sp3的激活。
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.