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Anke Stock, Helmut Sies

Thyroid Hormone Receptors Bind to an Element in the Connexin43 Promoter

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 ?/retinoid X receptor ? heterodimers than with vitamin D receptor/retinoid X receptor ? 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.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 381, 09/2000
Pages: 973 - 979

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