Novel human TEF-1 isoforms exhibit altered DNA binding and functional properties
Novel human TEF-1 isoforms exhibit altered DNA binding and functional properties
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DOI：
10.1021/bi991048w
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发表时间：
2000-03-28
期刊：
影响因子：
2.9
通讯作者：
Eberhardt, NL
中科院分区：
文献类型：
--
作者：
Jiang, SW;Trujillo, MA;Eberhardt, NL
转录增强因子-1(TEF-1)是TEA/ATTS结构域家族的成员。TEF-1与GT-IIC(GGAATG)、SphI(AGTATG)、SphII(AGCATG)和M-CAT(GGTATG)反应元件结合，参与多种基因的反式激活，包括SV40大T抗原、哺乳动物肌肉特异性基因和人绒毛膜生长抑素基因。此外，TEF-1可能通过与TATA结合蛋白(TBP)相互作用，阻止TBP与TATA盒结合，在胎盘细胞中扮演转录抑制因子的角色。在这里，我们描述了两个新的TEF-1亚型，TEF-1β和TEF-1伽马的克隆、组织特异性表达模式和功能鉴定。这些异构体很可能来自单个基因转录的mRNA的选择性剪接，并涉及紧随DNA结合域之后的区域的替换和/或插入。TEF-1β似乎像原型TEF-1一样分布广泛，命名为TEF-1α，而TEF-1伽马显示出较窄的组织特异性表达模式，包括胰腺、肾脏、骨骼肌和心肌。这些异构体之间相对有限的序列变化导致了它们的DNA结合和转录活性的显著变化。TEF-1β和TEF-1γ以更高的亲和力与GT-IIC序列结合，并比TEF-1α更有效地抑制HCS启动子，这些结果表明TEF-1的每个亚型可能在不同的组织中发挥独特的调节作用。
The transcriptional enhancer factor-1 (TEF-1) is a member of the TEA/ATTS domain family. TEF-1 binds to GT-IIC (GGAATG), SphI (AGTATG), SphII (AGCATG), and M-CAT (GGTATG) response elements and is involved in the transactivation of a variety of genes, including the SV40 large T antigen, mammalian muscle-specific genes, and human chorionic somatomammotropin genes. Also, TEF-1 acts as a transcriptional repressor in placental cells, possibly through interaction with the TATA binding protein (TBP), preventing TBP binding to the TATA box. Here we describe the cloning, tissue-specific expression pattern, and functional characterization of two novel TEF-1 isoforms, TEF-1 beta and TEF-1 gamma. These isoforms most likely arise from alternative splicing of mRNA transcribed from a single gene and involve substitutions and/or insertions in a region immediately following the DNA binding domain. TEF-1 beta appears to be widely distributed like the prototypic TEF-1, designated TEF-1 alpha, whereas TEF-1 gamma exhibits a narrower tissue-specific expression pattern that includes pancreas, kidney, and skeletal and heart muscle. The relatively limited sequence alterations among these isoforms cause significant changes in their DNA binding and transcriptional activities. TEF-1 beta and TEF-1 gamma bind to GT-IIC sequences with higher affinity and repress hCS promoter more efficiently than TEF-1 alpha, These results suggest that each TEF-1 isoform may play unique regulatory roles in various tissues.