Presence of Transcription Factor OCT4 Limits Interferon-tau Expression during the Pre-attachment Period in Sheep.
Presence of Transcription Factor OCT4 Limits Interferon-tau Expression during the Pre-attachment Period in Sheep.
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DOI：
10.5713/ajas.2012.12462
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Imakawa K
中科院分区：
文献类型：
--
作者：
Kim MS;Sakurai T;Bai H;Bai R;Sato D;Nagaoka K;Chang KT;Godkin JD;Min KS;Imakawa K
干扰素-tau（IFNT）被认为是反刍动物中母体识别妊娠的孕体蛋白。我们和其他人已经观察到，OCT 4的表达持续在反刍动物的滋养外胚层，因此，CDX 2和OCT 4共存的早期阶段的概念发展。本研究的目的是检查CDX 2和OCT 4与其他转录因子一起评估时对IFNT基因转录的影响。用羊IFNT（~ 654-bp）-荧光素酶报告基因（~ 654-IFNT-Luc）构建体和几种转录因子表达质粒共转染人绒毛膜癌JEG-3细胞。与单独转染构建体相比，用Cdx 2、Ets 2和Jun共转染报告构建体使-654-IFNT-Luc的转录增加约12倍。当细胞最初用Oct 4（0 h）转染，随后在24 h后用Cdx 2、Ets 2和/或Jun转染时，-654-IFNT-Luc的表达降低至对照水平。OCT 4也抑制单独的CDX 2的刺激活性，但当CDX 2与JUN和/或ETS 2组合时不抑制。因此，当与其他转录因子组合时，OCT 4对CDX 2表现出很小的抑制活性。转录共激活因子CREB结合蛋白（CREBBP）的抑制剂12 S E1 A使CDX 2/ETS 2/JUN刺激的-654-IFNT-Luc表达降低约40%，表明最大表达需要形成适当的转录因子复合物。总之，OCT 4的存在最初可能会使IFNT表达最小化;然而，随着延长的进行，CDX 2的表达增加和转录复合物的形成导致IFNT表达大大增加，从而导致反刍动物妊娠的建立。
Interferon-tau (IFNT) is thought to be the conceptus protein that signals maternal recognition of pregnancy in ruminants. We and others have observed that OCT4 expression persists in the trophectoderm of ruminants; thus, both CDX2 and OCT4 coexist during the early stages of conceptus development. The aim of this study was to examine the effect of CDX2 and OCT4 on IFNT gene transcription when evaluated with other transcription factors. Human choriocarcinoma JEG-3 cells were cotransfected with an ovine IFNT (-654-bp)-luciferase reporter (-654-IFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with Cdx2, Ets2 and Jun increased transcription of -654-IFNT-Luc by about 12-fold compared with transfection of the construct alone. When cells were initially transfected with Oct4 (0 h) followed by transfection with Cdx2, Ets2 and/or Jun 24 h later, the expression of -654-IFNT-Luc was reduced to control levels. OCT4 also inhibited the stimulatory activity of CDX2 alone, but not when CDX2 was combined with JUN and/or ETS2. Thus, when combined with the other transcription factors, OCT4 exhibited little inhibitory activity towards CDX2. An inhibitor of the transcriptional coactivator CREB binding protein (CREBBP), 12S E1A, reduced CDX2/ETS2/JUN stimulated -654-IFNT-Luc expression by about 40%, indicating that the formation of an appropriate transcription factor complex is required for maximum expression. In conclusion, the presence of OCT4 may initially minimize IFNT expression; however, as elongation proceeds, the increasing expression of CDX2 and formation of the transcription complex leads to greatly increased IFNT expression, resulting in pregnancy establishment in ruminants.
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