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Sterol regulatory element-binding proteins are regulators of the rat thyroid peroxidase gene in thyroid cells

Rauer, Christine ; Ringseis, Robert ; Rothe, Susanne ; Wen, Gaiping ; Eder, Klaus


Originalveröffentlichung: (2014) PLoS ONE 9(3):e91265 doi:10.1371/journal.pone.0091265
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URN: urn:nbn:de:hebis:26-opus-111519
URL: http://geb.uni-giessen.de/geb/volltexte/2014/11151/

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Sammlung: Open Access - Publikationsfonds
Universität Justus-Liebig-Universität Gießen
Institut: Institut Für Tierernährung und Ernährungsphysiologie
Fachgebiet: Agrarwissenschaften und Umweltmanagement
DDC-Sachgruppe: Landwirtschaft
Dokumentart: Aufsatz
Sprache: Englisch
Erstellungsjahr: 2014
Publikationsdatum: 27.10.2014
Kurzfassung auf Englisch: Sterol regulatory element-binding proteins (SREBPs)-1c and -2, which were initially discovered as master transcriptional regulators of lipid biosynthesis and uptake, were recently identified as novel transcriptional regulators of the sodium-iodide symporter gene in the thyroid, which is essential for thyroid hormone synthesis. Based on this observation that SREBPs play a role for thyroid hormone synthesis, we hypothesized that another gene involved in thyroid hormone synthesis, the thyroid peroxidase (TPO) gene, is also a target of SREBP-1c and -2. Thyroid epithelial cells treated with 25-hydroxycholesterol, which is known to inhibit SREBP activation, had about 50% decreased mRNA levels of TPO. Similarly, the mRNA level of TPO was reduced by about 50% in response to siRNA mediated knockdown of both, SREBP-1 and SREBP-2. Reporter gene assays revealed that overexpression of active SREBP-1c and -2 causes a strong transcriptional activation of the rat TPO gene, which was localized to an approximately 80 bp region in the intron 1 of the rat TPO gene. In vitro- and in vivo-binding of both, SREBP-1c and SREBP-2, to this region in the rat TPO gene could be demonstrated using gel-shift assays and chromatin immunoprecipitation. Mutation analysis of the 80 bp region of rat TPO intron 1 revealed two isolated and two overlapping SREBP-binding elements from which one, the overlapping SRE+609/InvSRE+614, was shown to be functional in reporter gene assays. In connection with recent findings that the rat NIS gene is also a SREBP target gene in the thyroid, the present findings suggest that SREBPs may be possible novel targets for pharmacological modulation of thyroid hormone synthesis.
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