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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Thyroid Hormone Receptors Bind to an Element in the Connexin43 Promoter

Anke Stock / Helmut Sies

Citation Information: Biological Chemistry. Volume 381, Issue 9-10, Pages 973–979, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2000.120, July 2005

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Thyroid hormones stimulate gap junctional communication in rat liver WB-F344 epithelial cells, elevating connexin43 mRNA and protein levels. In the present work we analysed connexin43 expression in liver and heart samples from thyroid hormone-treated Wistar rats. Connexin43 mRNA was elevated 2.1-fold in rat liver samples as compared to controls, while there was no change in heart. Thyroid hormone response elements in the rat connexin43 promoter region were examined; a candidate sequence, including a binding site for ligand-dependent transcription factors, was identified at position −480 to −464. This putative regulatory element, rCx−480, contains a direct repeat structure separated by three base pairs (DR3-type element). In electrophoretic mobility shift assays using in vitro translated proteins, the rCx−480 element formed stronger complexes with thyroid hormone receptor α/retinoid X receptor α heterodimers than with vitamin D receptor/retinoid X receptor α heterodimers. In transfected Cos-7 cells, promoter activation was observed via this element after treatment with 3,3′,5-triiodo-L-thyronine. Loss of binding was seen when the 3′ half-site or the spacer region of the rCx−480 element were experimentally mutated, while a stronger binding was observed with mutations introduced in the 5′ halfsite.

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