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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Zinc-finger protein-targeted gene regulation: Genomewide single-gene specificity.
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Zinc-finger protein-targeted gene regulation: Genomewide single-gene specificity.

机译：锌指蛋白靶向的基因调控：全基因组单基因特异性。

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摘要

Zinc-finger protein transcription factors (ZFP TFs) can be designed to control the expression of any desired target gene, and thus provide potential therapeutic tools for the study and treatment of disease. Here we report that a ZFP TF can repress target gene expression with single-gene specificity within the human genome. A ZFP TF repressor that binds an 18-bp recognition sequence within the promoter of the endogenous CHK2 gene gives a >10-fold reduction in CHK2 mRNA and protein. This level of repression was sufficient to generate a functional phenotype, as demonstrated by the loss of DNA damage-induced CHK2-dependent p53 phosphorylation. We determined the specificity of repression by using DNA microarrays and found that the ZFP TF repressed a single gene (CHK2) within the monitored genome in two different cell types. These data demonstrate the utility of ZFP TFs as precise tools for target validation, and highlight their potential as clinical therapeutics.
机译：锌指蛋白转录因子（ZFP TF）可以设计为控制任何所需靶基因的表达，从而为疾病的研究和治疗提供潜在的治疗工具。在这里，我们报道ZFP TF可以抑制人类基因组中具有单基因特异性的靶基因表达。 ZFP TF阻遏物与内源性CHK2基因启动子内的18 bp识别序列结合，可使CHK2 mRNA和蛋白质的含量降低10倍以上。这种抑制水平足以产生功能表型，如DNA损伤诱导的依赖CHK2的p53磷酸化作用的丧失所证明。我们通过使用DNA微阵列确定了抑制作用的特异性，并发现ZFP TF在两种不同的细胞类型中抑制了受监测基因组中的单个基因（CHK2）。这些数据证明了ZFP TF作为精确的靶标验证工具的实用性，并突出了其作为临床治疗剂的潜力。

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