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Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality
Published on: June 2, 2023
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Intracellular zinc-dependent TAS2R8 gene expression through CTCF activation
Tsuyoshi Kojima1, Toyonobu Maeda1,2, Atsuko Suzuki2
1Departments of Oral Rehabilitation, Ohu University Graduate School of Dentistry.
Biomedical Research (Tokyo, Japan)
|October 19, 2020
Summary
Zinc deficiency impacts bitter taste perception by altering TAS2R8 gene expression. This study reveals that zinc is crucial for TAS2R8 promoter activity, mediated by CTCF binding.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Taste-2 receptors (TAS2Rs) are G-protein coupled receptors (GPCRs) responsible for bitter taste perception.
- The role of essential minerals, such as zinc, in regulating TAS2R gene expression is not fully understood.
Purpose of the Study:
- To investigate the effect of zinc deficiency on the expression of TAS2R genes.
- To identify the molecular mechanisms underlying zinc's influence on TAS2R promoter activity.
Main Methods:
- Utilized Ca9-22 oral squamous cell carcinoma cells cultured with or without zinc.
- Employed luciferase reporter assays to measure TAS2R promoter activity.
- Conducted truncation/deletion analyses and chromatin immunoprecipitation (ChiP) assays to identify key regulatory elements and protein interactions.
Main Results:
- Zinc deprivation significantly inhibited the promoter activity of the TAS2R8 gene, but not TAS2R7 or TAS2R42.
- Intracellular zinc chelation using TPEN also reduced TAS2R8 promoter activity.
- A critical region (-1152 to -925 bp) of the TAS2R8 promoter, containing a CTCF binding motif, was identified as essential for zinc dependency.
- Zinc deficiency disrupted CTCF binding to this critical promoter region.
Conclusions:
- Zinc is essential for regulating TAS2R8 gene expression, a key receptor in bitter taste perception.
- The CCCTC-binding factor (CTCF) plays a critical role in mediating zinc-dependent regulation of TAS2R8.
- These findings suggest a novel link between zinc homeostasis and bitter taste signaling pathways.
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