HNF4α is required for Tkfc promoter activation by ChREBP.

IF 1.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioscience, Biotechnology, and Biochemistry Pub Date : 2024-07-22 DOI:10.1093/bbb/zbae067

Rena Tsukamoto, Kyoko Watanabe, Manami Kodaka, Masamori Iwase, Haruhiko Sakiyama, Yusuke Inoue, Tsukasa Suzuki, Yuji Yamamoto, Makoto Shimizu, Ryuichiro Sato, Jun Inoue

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引用次数: 0

Abstract

Triokinase/FMN cyclase (Tkfc) is involved in fructose metabolism and is responsible for the phosphorylation of glyceraldehyde to glyceraldehyde-3-phosphate. In this study, we showed that refeeding induced hepatic expression of Tkfc in mice. Luciferase reporter gene assays using the Tkfc promoter revealed the existence of 2 hepatocyte nuclear factor 4α (HNF4α)-responsive elements (HNF4RE1 and HNF4RE2) and 1 carbohydrate-responsive element-binding protein (ChREBP)-responsive element (ChoRE1). Deletion and mutation of HNF4RE1 and HNF4RE2 or ChoRE1 abolished HNF4α and ChREBP responsiveness, respectively. HNF4α and ChREBP synergistically stimulated Tkfc promoter activity. ChoRE1 mutation attenuated but maintained HNF4α responsiveness, whereas HNF4RE1 and HNF4RE2 mutations abolished ChREBP responsiveness. Moreover, Tkfc promoter activity stimulation by ChREBP was attenuated upon HNF4α knockdown. Furthermore, Tkfc expression was decreased in the livers of ChREBP-/- and liver-specific HNF4-/- (Hnf4αΔHep) mice. Altogether, our data indicate that Tkfc is a target gene of ChREBP and HNF4α, and Tkfc promoter activity stimulation by ChREBP requires HNF4α.

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HNF4α 是 ChREBP 激活 Tkfc 启动子所必需的。

三酮酸酶/FMN环化酶（Tkfc）参与果糖代谢，负责将甘油醛磷酸化为甘油醛-3-磷酸。在这项研究中，我们发现再喂食会诱导小鼠肝脏表达 Tkfc。使用 Tkfc 启动子进行的荧光素酶报告基因检测发现，存在两个肝细胞核因子 4α (HNF4α) 响应元件（HNF4RE1 和 HNF4RE2）和一个碳水化合物响应元件结合蛋白 (ChREBP) 响应元件（ChoRE1）。HNF4RE1和HNF4RE2或ChoRE1的缺失和突变分别取消了HNF4α和ChREBP的响应性。HNF4α和ChREBP协同刺激Tkfc启动子的活性。ChoRE1突变减弱但维持了HNF4α的反应性，而HNF4RE1和HNF4RE2突变则取消了ChREBP的反应性。此外，HNF4α基因敲除后，ChREBP对Tkfc启动子活性的刺激减弱。此外，ChREBP-/-和肝特异性HNF4-/-（Hnf4αΔHep）小鼠肝脏中的Tkfc表达量减少。总之，我们的数据表明，Tkfc是ChREBP和HNF4α的靶基因，ChREBP对Tkfc启动子活性的刺激需要HNF4α。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioscience, Biotechnology, and Biochemistry 生物-生化与分子生物学

CiteScore

3.50

自引率

0.00%

发文量

183

审稿时长

1 months

期刊介绍： Bioscience, Biotechnology, and Biochemistry publishes high-quality papers providing chemical and biological analyses of vital phenomena exhibited by animals, plants, and microorganisms, the chemical structures and functions of their products, and related matters. The Journal plays a major role in communicating to a global audience outstanding basic and applied research in all fields subsumed by the Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA).