Transcriptional control of IFNT expression.
Transcriptional control of IFNT expression.
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DOI：
10.1530/rep-17-0330
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Imakawa K
中科院分区：
文献类型：
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作者：
Ezashi T;Imakawa K
一旦干扰素-tau（IFNT）被鉴定为绵羊和牛中的I型IFN并表征其功能，就进行了许多研究以阐明该基因家族的转录调控。转染研究进行了很大程度上与人绒毛膜癌细胞系确定的IFNT基因的调控区，似乎负责滋养层特异性表达。关键的发现是认识到转录因子ETS 2结合到牛IFNT的5/UTR内的近端区域，并充当强反式激活因子。不久之后，其他转录因子被确定为合作伙伴。ETS 2结合位点和附近的AP 1位点能够响应来自母体子宫因子的细胞内信号传导。AP 1位点也用作牛IFNT基因之一中的加塔结合位点。含同源框的转录因子DLX 3与ETS 2组合增强IFNT表达。CDX 2也被鉴定为反式激活因子，其结合至主要ETS 2增强子位点上游的单独位点。CDX 2通过修饰基因的组蛋白乙酰化状态参与IFNT表观遗传调控。IFNT在孕体附着于子宫内膜时的下调似乎与EOMES表达的增加和其他转录辅激活因子的丢失相关。总之，IFNT转录调控的研究为滋养层细胞特异性表达的调控框架和母体识别妊娠的关键表达模式提供了机制证据。
Once interferon-tau (IFNT) had been identified as a Type I IFN in sheep and cattle and its functions characterized, numerous studies were conducted to elucidate transcriptional regulation of this gene family. Transfection studies performed largely with human choriocarcinoma cell lines identified regulatory regions of the IFNT gene that appeared responsible for trophoblast-specific expression. The key finding was the recognition that the transcription factor ETS2 bound to a proximal region within the 5/UTR of a bovine IFNT and acted as a strong transactivator. Soon after other transcription factors were identified as cooperative partners. The ETS2-binding site and the nearby AP1 site enable response to intracellular signaling from maternal uterine factors. The AP1 site also serves as a GATA binding site in one of the bovine IFNT genes. The homeobox-containing transcription factor, DLX3, augments IFNT expression combinatorially with ETS2. CDX2 has also been identified as transactivator that binds to a separate site upstream of the main ETS2 enhancer site. CDX2 participates in IFNT epigenetic regulation by modifying histone acetylation status of the gene. The IFNT down-regulation at the time of the conceptus attachment to the uterine endometrium appears correlated with the increased EOMES expression and the loss of other transcription coactivators. Altogether, the studies of transcriptional control of IFNT have provided mechanistic evidence of the regulatory framework of trophoblast-specific expression and critical expression pattern for maternal recognition of pregnancy.