Journal article

Publication year: 2014

Journal: PLoS ONE

Volume number: 9

Issue number: 3

ISSN: 1932-6203

Open access status: Gold

DOI Link: https://doi.org/10.1371/journal.pone.0091265

Publisher: Public Library of Science

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.

Harvard Citation style: Rauer, C., Ringseis, R., Rothe, S., Wen, G. and Eder, K. (2014) Sterol Regulatory Element-Binding Proteins Are Regulators of the Rat Thyroid Peroxidase Gene in Thyroid Cells, PLoS ONE, 9(3), Article e91265. https://doi.org/10.1371/journal.pone.0091265

APA Citation style: Rauer, C., Ringseis, R., Rothe, S., Wen, G., & Eder, K. (2014). Sterol Regulatory Element-Binding Proteins Are Regulators of the Rat Thyroid Peroxidase Gene in Thyroid Cells. PLoS ONE. 9(3), Article e91265. https://doi.org/10.1371/journal.pone.0091265