Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXR
Farnesoid x receptor (FXR) is a nuclear bile acid receptor that belongs to the nuclear receptor superfamily. It plays an essential role in bile acid biosynthesis, lipid and glucose metabolism, liver regeneration, and vertical sleeve gastrectomy. A loss of the <i>FXR</i> gene or dysregula...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/1980 |
| _version_ | 1797479486549131264 |
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| author | Eun Young Kim Jae Man Lee |
| author_facet | Eun Young Kim Jae Man Lee |
| author_sort | Eun Young Kim |
| collection | DOAJ |
| description | Farnesoid x receptor (FXR) is a nuclear bile acid receptor that belongs to the nuclear receptor superfamily. It plays an essential role in bile acid biosynthesis, lipid and glucose metabolism, liver regeneration, and vertical sleeve gastrectomy. A loss of the <i>FXR</i> gene or dysregulations of FXR-mediated gene expression are associated with the development of progressive familial intrahepatic cholestasis, tumorigenesis, inflammation, and diabetes mellitus. Magnesium ion (Mg<sup>2+</sup>) is essential for mammalian physiology. Over 600 enzymes are dependent on Mg<sup>2+</sup> for their activity. Here, we show that the <i>Trpm6</i> gene encoding a Mg<sup>2+</sup> channel is a direct FXR target gene in the intestinal epithelial cells of mice. FXR expressed in the intestinal epithelial cells is absolutely required for sustaining a basal expression of intestinal <i>Trpm6</i> that can be robustly induced by the treatment of GW4064, a synthetic FXR agonist. Analysis of FXR ChIP-seq data revealed that intron regions of <i>Trpm6</i> contain two prominent FXR binding peaks. Among them, the proximal peak from the transcription start site contains a functional inverted repeat 1 (IR1) response element that directly binds to the FXR-RXRα heterodimer. Based on these results, we proposed that an intestinal FXR-TRPM6 axis may link a bile acid signaling to Mg<sup>2+</sup> homeostasis. |
| first_indexed | 2024-03-09T21:46:35Z |
| format | Article |
| id | doaj.art-fce1f5e1015042d7aad8bec326c3f12f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:46:35Z |
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| spelling | doaj.art-fce1f5e1015042d7aad8bec326c3f12f2023-11-23T20:17:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234198010.3390/ijms23041980Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXREun Young Kim0Jae Man Lee1Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, KoreaDepartment of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, KoreaFarnesoid x receptor (FXR) is a nuclear bile acid receptor that belongs to the nuclear receptor superfamily. It plays an essential role in bile acid biosynthesis, lipid and glucose metabolism, liver regeneration, and vertical sleeve gastrectomy. A loss of the <i>FXR</i> gene or dysregulations of FXR-mediated gene expression are associated with the development of progressive familial intrahepatic cholestasis, tumorigenesis, inflammation, and diabetes mellitus. Magnesium ion (Mg<sup>2+</sup>) is essential for mammalian physiology. Over 600 enzymes are dependent on Mg<sup>2+</sup> for their activity. Here, we show that the <i>Trpm6</i> gene encoding a Mg<sup>2+</sup> channel is a direct FXR target gene in the intestinal epithelial cells of mice. FXR expressed in the intestinal epithelial cells is absolutely required for sustaining a basal expression of intestinal <i>Trpm6</i> that can be robustly induced by the treatment of GW4064, a synthetic FXR agonist. Analysis of FXR ChIP-seq data revealed that intron regions of <i>Trpm6</i> contain two prominent FXR binding peaks. Among them, the proximal peak from the transcription start site contains a functional inverted repeat 1 (IR1) response element that directly binds to the FXR-RXRα heterodimer. Based on these results, we proposed that an intestinal FXR-TRPM6 axis may link a bile acid signaling to Mg<sup>2+</sup> homeostasis.https://www.mdpi.com/1422-0067/23/4/1980nuclear receptorFXRbile acid<i>Trpm6</i>small intestinecolon |
| spellingShingle | Eun Young Kim Jae Man Lee Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXR International Journal of Molecular Sciences nuclear receptor FXR bile acid <i>Trpm6</i> small intestine colon |
| title | Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXR |
| title_full | Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXR |
| title_fullStr | Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXR |
| title_full_unstemmed | Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXR |
| title_short | Transcriptional Control of <i>Trpm6</i> by the Nuclear Receptor FXR |
| title_sort | transcriptional control of i trpm6 i by the nuclear receptor fxr |
| topic | nuclear receptor FXR bile acid <i>Trpm6</i> small intestine colon |
| url | https://www.mdpi.com/1422-0067/23/4/1980 |
| work_keys_str_mv | AT eunyoungkim transcriptionalcontrolofitrpm6ibythenuclearreceptorfxr AT jaemanlee transcriptionalcontrolofitrpm6ibythenuclearreceptorfxr |