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首页> 外文期刊>Biochemistry >INHIBITION OF IN VITRO TRANSCRIPTION BY A TRIPLEX-FORMING OLIGONUCLEOTIDE TARGETED TO HUMAN C-MYC P2 PROMOTER
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INHIBITION OF IN VITRO TRANSCRIPTION BY A TRIPLEX-FORMING OLIGONUCLEOTIDE TARGETED TO HUMAN C-MYC P2 PROMOTER

机译：靶向人C-MYC P2启动子的三链形成寡核苷酸抑制体外转录

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摘要

Tripler-forming oligonucleotides (TFOs) have been shown to bind in a sequence-specific manner to polypurine/polypyrimidine sequences in several human gene promoters, including the c-myc P1 promoter. TFOs have been shown to inhibit transcription in vitro and the expression of target genes in cell culture. The human c-myc protooncogene contains a 23 base pair purine-pyrimidine-rich motif (-62 to -40) within its predominant promoter, P2, that is a potential target for purine-purine-pyrimidine tripler formation. Using electrophoretic mobility shift analysis (EMSA) and competition experiments, we have demonstrated that a MAZ (myc-associated zinc finger protein) consensus sequence is capable of competing with the purine-pyrimidine motif for the binding of a HeLa nuclear protein. We have shown the formation of an intermolecular tripler using a 23-base purine-rich oligonucleotide antiparallel to the purine-rich target sequence, DNase I footprinting was performed to confirm the exact location of tripler formation. Tripler formation by this oligonucleotide prevents binding of a HeLa nuclear protein (presumably MAZ) to the target site. We have also shown that the P2-targeted TFO is a potent and specific inhibitor of c-myc transcription in vitro. These data demonstrate that this novel TFO inhibits transcription of the c-myc P2 promoter. We propose that the P2-targeted TFO has its effect by blocking the binding of the regulatory factor MAZ.
机译：已显示形成三链体的寡核苷酸（TFO）以序列特异性的方式与包括c-myc P1启动子在内的几种人类基因启动子中的聚嘌呤/聚嘧啶序列结合。 TFO已显示在体​​外抑制转录和在细胞培养物中抑制靶基因的表达。人c-myc原癌基因在其主要启动子P2中含有23个碱基对的富含嘌呤-嘧啶的基序（-62至-40），这是嘌呤-嘌呤-嘧啶三聚体形成的潜在靶标。使用电泳迁移率变动分析（EMSA）和竞争实验，我们证明了MAZ（myc相关的锌指蛋白）共有序列能够与嘌呤-嘧啶基序竞争与HeLa核蛋白的结合。我们已经显示了使用与富含嘌呤的靶序列反平行的富含23个碱基的嘌呤的寡核苷酸形成分子间三聚体，进行DNase I印迹以确认三聚体形成的确切位置。该寡核苷酸形成的三链体阻止了HeLa核蛋白（可能是MAZ）与靶位的结合。我们还显示，靶向P2的TFO是体外c-myc转录的有效和特异性抑制剂。这些数据证明，该新型TFO抑制c-myc P2启动子的转录。我们建议靶向P2的TFO通过阻断调节因子MAZ的结合而发挥作用。

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