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小鼠Oct-1转录因子一种新亚型的克隆、基因组结构、表达及其对β-酪蛋白启动子活性的影响

Cloning, genomic organization, expression, and effect on beta-casein promoter activity of a novel isoform of the mouse Oct-1 transcription factor.

作者信息

Zhao Feng-Qi, Zheng Yucai, Dong Bing, Oka Takami

机构信息

Lactation and Mammary Gland Biology Group, Department of Animal Science, University of Vermont, Burlington, VT 05405, USA.

出版信息

Gene. 2004 Feb 4;326:175-87. doi: 10.1016/j.gene.2003.10.023.

DOI:10.1016/j.gene.2003.10.023
PMID:14729276
Abstract

The ubiquitously expressed transcription factor Oct-1, a member of the POU domain factors, is involved in the regulation of expression of many tissue-specific and house-keeping genes. Multiple alternatively spliced isoforms of Oct-1 have been identified in human and mouse cells. The expression patterns of these isoforms and the analysis of their genomic organization and structure have suggested that the structural variation of Oct-1 isoforms may be important in conferring target and tissue specificity to its transcriptional activity. In this study, we have cloned and sequenced a new mouse Oct-1 isoform, named mOct-1Z. This novel isoform differs markedly at the C-terminus from the previously identified Oct-1 isoforms A, B, and C. It is generated by alternative splicing from the Oct-1 gene and its transcript exhibits a frameshift followed by an early stop codon, thus, its predicted protein has a distinct, much shorter C-terminal tail. However, this truncated isoform could still effectively bind to a consensus Oct-1 motif oligonucleotide and, like Oct-1B, activated the basal promoter activity of the mouse beta-casein gene. Oct-1Z is another ubiquitously expressed Oct-1 isoform, its transcript being detected in all mouse tissues examined, including the mammary gland, liver, lung, kidney, spleen, small intestine mucosa, uterus, and ovary.

摘要

普遍表达的转录因子Oct-1是POU结构域因子家族的成员,参与许多组织特异性基因和管家基因表达的调控。在人和小鼠细胞中已鉴定出Oct-1的多种可变剪接异构体。这些异构体的表达模式及其基因组组织和结构分析表明,Oct-1异构体的结构变异可能对赋予其转录活性的靶标和组织特异性很重要。在本研究中,我们克隆并测序了一种新的小鼠Oct-1异构体,命名为mOct-1Z。这种新的异构体在C末端与先前鉴定的Oct-1异构体A、B和C有明显差异。它是由Oct-1基因的可变剪接产生的,其转录本表现出移码,随后是一个早期终止密码子,因此,其预测的蛋白质具有独特的、短得多的C末端尾巴。然而,这种截短的异构体仍然可以有效地结合到一致的Oct-1基序寡核苷酸上,并且像Oct-1B一样,激活小鼠β-酪蛋白基因的基础启动子活性。Oct-1Z是另一种普遍表达的Oct-1异构体,在所有检测的小鼠组织中都能检测到其转录本,包括乳腺、肝脏、肺、肾脏、脾脏、小肠黏膜、子宫和卵巢。

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