TBX6 对嗅觉受体 OR51B5 的转录调控。

IF 5 2区 生物学 Q2 CELL BIOLOGY American journal of physiology. Cell physiology Pub Date : 2024-10-28 DOI:10.1152/ajpcell.00464.2024
Jiyun Roh, Wesuk Kang, Suhjin Yang, Dabin Choi, Taesun Park
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引用次数: 0

摘要

嗅觉受体(ORs)是一种 G 蛋白偶联受体,主要在嗅觉组织中表达,有助于感知气味。有趣的是,在皮肤等非嗅觉组织中也检测到了嗅觉受体,它们能调节胶原蛋白合成等过程。本研究旨在分析OR家族51亚族B成员5(OR51B5)的启动子,并确定与之结合的转录因子,以了解OR51B5表达的潜在调控机制。我们考察了转录起始位点上游横跨2000个碱基对的启动子区域,并进行了缺失分析,结果显示核心启动子包括-153至-111个碱基对的区域。利用各种候选转录因子进行的荧光素酶试验表明,过表达或敲除T-Box转录因子6(TBX6)可显著调节OR51B5启动子的活性,而其他候选转录因子则无明显影响。此外,我们还利用定点突变和电泳迁移实验验证了TBX6与OR51B5启动子的结合。这项研究首次揭示了 TBX 转录因子在调节哺乳动物 OR 基因表达中的作用,可能对治疗相关疾病有意义。
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Transcriptional regulation of olfactory receptor OR51B5 by the TBX6.

Olfactory receptors (ORs) are G protein-coupled receptors primarily expressed in olfactory tissue, facilitating the perception of odors. Interestingly, they have also been detected in non-olfactory tissues such as the skin, where they regulate processes like collagen synthesis. This study aimed to analyze the promoter of the OR family 51 subfamily B member 5 (OR51B5) and identify the transcription factors that bind to it to understand the potential regulatory mechanisms for OR51B5 expression. We examined the promoter region spanning 2,000 base pairs upstream of the transcription start site and conducted a deletion analysis, revealing that the core promoter encompasses the region from -153 to -111 base pairs. A luciferase assay using various candidate transcription factors showed that the overexpression or knockdown of T-Box Transcription Factor 6 (TBX6) significantly regulated OR51B5 promoter activity, while other candidate transcription factors had no significant effect. Additionally, we validated TBX6 binding to the OR51B5 promoter using site-directed mutation and electrophoretic mobility shift assays. This study is the first to uncover the role of TBX transcription factors in regulating OR gene expression in mammals, which may have implications for treating related disorders.

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来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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