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首页> 外文期刊>Genomics >Overlapping and distinct transcriptional regulator properties of the GLI1 and GLI2 oncogenes.
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Overlapping and distinct transcriptional regulator properties of the GLI1 and GLI2 oncogenes.

机译:GLI1和GLI2癌基因的重叠和独特的转录调节特性。

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The GLI transcription factors mediate the hedgehog signal in development and carcinogenesis. Basal cell carcinoma can be caused by overexpression of either GLI1 or GLI2. Though GLI1 and GLI2 have identical or very similar DNA binding specificities, some of their activities are overlapping, some are clearly distinct. We analyzed target gene specificities of GLI1 and constitutively active GLI2 (GLI2DeltaN) by global expression profiling in an inducible, well-characterized HaCaT keratinocyte expression system. Four hundred fifty-six genes up- or downregulated at least twofold were identified. GLI target gene profiles correlated well with the biological activities of these transcription factors in hair follicles and basal cell carcinoma. Upregulation of largely overlapping sets of target genes was effected by both factors, repression occurred predominantly in response to GLI2. Also, significant quantitative differences in response to GLI1 and GLI2DeltaN were found for a small number of activated genes. Since we have not detected a putative processed GLI2 repressor, these results point to specific but indirect target gene repression by GLI2DeltaN via preferential activation of one or more negative regulators.
机译:GLI转录因子在发育和致癌过程中介导刺猬信号。基底细胞癌可能由GLI1或GLI2的过表达引起。尽管GLI1和GLI2具有相同或非常相似的DNA结合特异性,但它们的某些活动是重叠的,而某些活动却明显不同。我们通过在可诱导的,特征明确的HaCaT角质形成细胞表达系统中的全局表达谱分析来分析GLI1和组成型活性GLI2(GLI2DeltaN)的靶基因特异性。鉴定出上调或下调至少两倍的456个基因。 GLI靶基因谱与这些转录因子在毛囊和基底细胞癌中的生物学活性密切相关。靶基因在很大程度上重叠的套受到两个因素的影响,抑制主要发生在对GLI2的反应中。此外,发现少量激活基因对GLI1和GLI2DeltaN的响应存在明显的定量差异。由于我们尚未检测到推定的加工过的GLI2阻遏物,因此这些结果表明GLI2DeltaN通过优先激活一个或多个负调控子来特异性但间接地抑制靶基因。

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