Online-Ressource | |
Verfasst von: | Matsuo, Shunsuke [VerfasserIn] |
Ogawa, Masayuki [VerfasserIn] | |
Muckenthaler, Martina [VerfasserIn] | |
Mizui, Yumiko [VerfasserIn] | |
Sasaki, Shota [VerfasserIn] | |
Fujimura, Takafumi [VerfasserIn] | |
Takizawa, Masayuki [VerfasserIn] | |
Ariga, Nagayuki [VerfasserIn] | |
Ozaki, Hiroaki [VerfasserIn] | |
Sakaguchi, Masakiyo [VerfasserIn] | |
Gonzalez, Frank J. [VerfasserIn] | |
Inoue, Yusuke [VerfasserIn] | |
Titel: | Hepatocyte nuclear factor 4α controls iron metabolism and regulates transferrin receptor 2 in mouse liver |
Verf.angabe: | Shunsuke Matsuo, Masayuki Ogawa, Martina U. Muckenthaler, Yumiko Mizui, Shota Sasaki, Takafumi Fujimura, Masayuki Takizawa, Nagayuki Ariga, Hiroaki Ozaki, Masakiyo Sakaguchi, Frank J. Gonzalez, and Yusuke Inoue |
E-Jahr: | 2015 |
Jahr: | November 2, 2015 |
Umfang: | 12 S. |
Fussnoten: | Gesehen am 09.06.2020 |
Titel Quelle: | Enthalten in: JBC papers in press |
Ort Quelle: | Bethesda, MD. : American Soc. for Biochemistry and Molecular Biology, 2003 |
Jahr Quelle: | 2015 |
Band/Heft Quelle: | 290(2015), 52, Seite 30855-30865 |
ISSN Quelle: | 1083-351X |
Abstract: | Iron is an essential element in biological systems, but excess iron promotes the formation of reactive oxygen species, resulting in cellular toxicity. Several iron-related genes are highly expressed in the liver, a tissue in which hepatocyte nuclear factor 4α (HNF4α) plays a critical role in controlling gene expression. Therefore, the role of hepatic HNF4α in iron homeostasis was examined using liver-specific HNF4α-null mice (Hnf4aΔH mice). Hnf4aΔH mice exhibit hypoferremia and a significant change in hepatic gene expression. Notably, the expression of transferrin receptor 2 (Tfr2) mRNA was markedly decreased in Hnf4aΔH mice. Promoter analysis of the Tfr2 gene showed that the basal promoter was located at a GC-rich region upstream of the transcription start site, a region that can be transactivated in an HNF4α-independent manner. HNF4α-dependent expression of Tfr2 was mediated by a proximal promoter containing two HNF4α-binding sites located between the transcription start site and the translation start site. Both the GC-rich region of the basal promoter and the HNF4α-binding sites were required for maximal transactivation. Moreover, siRNA knockdown of HNF4α suppressed TFR2 expression in human HCC cells. These results suggest that Tfr2 is a novel target gene for HNF4α, and hepatic HNF4α plays a critical role in iron homeostasis. |
DOI: | doi:10.1074/jbc.M115.694414 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt. Volltext ; Verlag: https://doi.org/10.1074/jbc.M115.694414 |
Volltext: http://www.jbc.org/content/290/52/30855 | |
DOI: https://doi.org/10.1074/jbc.M115.694414 | |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | hepcidin |
HNF4α | |
hypoferremia | |
iron metabolism | |
liver | |
nuclear receptor | |
transcription regulation | |
transferrin | |
transferrin receptor 2 | |
K10plus-PPN: | 1700202871 |
Verknüpfungen: | → Zeitschrift |