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首页> 外文期刊>Molecular and Cellular Biology >Differential Interactions of Specific Nuclear Factor I Isoforms with the Glucocorticoid Receptor and STAT5 in the Cooperative Regulation of WAP Gene Transcription
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Differential Interactions of Specific Nuclear Factor I Isoforms with the Glucocorticoid Receptor and STAT5 in the Cooperative Regulation of WAP Gene Transcription

机译：WAP基因转录的合作调控中特定的核因子同工型与糖皮质激素受体和STAT5的差异相互作用。

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The distal region (?830 to ?720 bp) of the rat whey acidic protein (WAP) gene contains a composite response element (CoRE), which has been demonstrated previously to confer mammary gland-specific and hormonally regulated WAP gene expression. Point mutations in the binding sites for specific transcription factors present within this CoRE have demonstrated the importance of both nuclear factor I (NFI) and STAT5 as well as cooperative interactions with the glucocorticoid receptor (GR) in the regulation of WAP gene expression in the mammary gland of transgenic mice. This study reports the characterization of NFI gene expression during mammary gland development and the identification and cloning of specific NFI isoforms (NFI-A4, NFI-B2, and NFI-X1) from the mouse mammary gland during lactation. Some but not all of these NFI isoforms synergistically activate WAP gene transcription in cooperation with GR and STAT5, as determined using transient cotransfection assays in JEG-3 cells. On both the WAP CoRE and the mouse mammary tumor virus long terminal repeat promoter, the NFI-B isoform preferentially activated gene transcription in cooperation with STAT5A and GR. In contrast, the NFI-A isoform suppressed GR and STAT cooperativity at the WAP CoRE. Finally, unlike their interaction with the NFI consensus binding site in the adenovirus promoter, the DNA-binding specificities of the three NFI isoforms to the palindromic NFI site in the WAP CoRE were not identical, which may partially explain the failure of the NFI-A isoform to cooperate with GR and STAT5A.
机译：大鼠乳清酸性蛋白（WAP）基因的远端区域（？830至？720 bp）包含复合反应元件（CoRE），先前已证明该成分可赋予乳腺特异性和激素调节的WAP基因表达。该CoRE中存在的特定转录因子结合位点的点突变表明，核因子I（NFI）和STAT5以及与糖皮质激素受体（GR）的协同相互作用在乳腺WAP基因表达调控中的重要性转基因小鼠的腺体。这项研究报告了乳腺发育过程中NFI基因表达的特征以及哺乳期小鼠乳腺中特定NFI亚型（NFI-A4，NFI-B2和NFI-X1）的鉴定和克隆。如在JEG-3细胞中使用瞬时共转染测定所确定的，这些NFI亚型中的一些但不是全部与GR和STAT5协同激活WAP基因转录。在WAP CoRE和小鼠乳腺肿瘤病毒长末端重复启动子上，NFI-B亚型与STAT5A和GR共同优先激活基因转录。相反，NFI-A同工型抑制了WAP CoRE的GR和STAT协同作用。最后，不同于它们与腺病毒启动子中NFI共有结合位点的相互作用，三种NFI亚型对WAP CoRE中回文NFI位点的DNA结合特异性不同，这可能部分解释了NFI-A的失败异构体与GR和STAT5A配合使用。

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