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首页> 外文期刊>Molecular and Cellular Biology >Repression of Virus-Induced Interferon A Promoters by Homeodomain Transcription Factor Ptx1
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Repression of Virus-Induced Interferon A Promoters by Homeodomain Transcription Factor Ptx1

机译：同源域转录因子Ptx1抑制病毒诱导的干扰素A启动子。

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Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by substitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regulatory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid system, we describe here the identification of a specific DNRE-binding protein, the pituitary homeobox 1 (Ptx1 or Pitx1). Ptx1 is detectable in different cell types that differentially express IFN-A genes, and the endogenous Ptx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 negatively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is required for this repression. After virus induction, the expression of the Ptx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to the differential transcriptional strength of the promoters of different IFN-A genes and that these genes may provide new targets for transcriptional regulation by a homeodomain transcription factor.
机译：病毒诱导后，干扰素A（IFN-A）基因差异表达。单个IFN-A基因的差异表达通过其启动子的近端阳性病毒反应元件A（VRE-A）中的取代以及远端负调控元件（DNRE）的存在来调节。 DNRE的功能特征是通过抑制VRE-A活性来特异性发挥作用。通过使用酵母单杂交系统，我们在这里描述特定的DNRE结合蛋白，垂体同源盒1（Ptx1或Pitx1）的鉴定。在差异表达IFN-A基因的不同细胞类型中可检测到Ptx1，并且内源性Ptx1蛋白与DNRE特异性结合。在病毒诱导后，Ptx1负调节含DNRE的IFN-A启动子的转录，而这种抑制作用需要Ptx1蛋白的C末端区域以及同源域。病毒诱导后，Ptx1反义RNA的表达导致内源性IFN-A基因转录的显着增加，并能够修饰单个IFN-A基因差异表达的模式。这些研究表明，Ptx1有助于不同IFN-A基因启动子的差异转录强度，并且这些基因可能为同源域转录因子的转录调控提供新的靶点。

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