Sterol regulatory element-binding proteins are regulators of the rat thyroid peroxidase gene in thyroid cells
dc.contributor.author | Rauer, Christine | |
dc.contributor.author | Ringseis, Robert | |
dc.contributor.author | Rothe, Susanne | |
dc.contributor.author | Wen, Gaiping | |
dc.contributor.author | Eder, Klaus | |
dc.date.accessioned | 2022-11-18T09:50:30Z | |
dc.date.available | 2014-10-27T14:14:39Z | |
dc.date.available | 2022-11-18T09:50:30Z | |
dc.date.issued | 2014 | |
dc.description.abstract | 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. | en |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-111519 | |
dc.identifier.uri | https://jlupub.ub.uni-giessen.de//handle/jlupub/9069 | |
dc.identifier.uri | http://dx.doi.org/10.22029/jlupub-8457 | |
dc.language.iso | en | de_DE |
dc.rights | Namensnennung 3.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by/3.0/ | * |
dc.subject.ddc | ddc:630 | de_DE |
dc.title | Sterol regulatory element-binding proteins are regulators of the rat thyroid peroxidase gene in thyroid cells | en |
dc.type | article | de_DE |
local.affiliation | FB 09 - Agrarwissenschaften, Ökotrophologie und Umweltmanagement | de_DE |
local.opus.fachgebiet | Agrarwissenschaften und Umweltmanagement | de_DE |
local.opus.id | 11151 | |
local.opus.institute | Institut Für Tierernährung und Ernährungsphysiologie | de_DE |
local.source.freetext | PLoS ONE 9(3):e91265 | de_DE |
local.source.uri | https://doi.org/10.1371/journal.pone.0091265 |
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