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 alpha/retinoid X receptor alpha heterodimers than with vitamin D receptor/retinoid X receptor alpha 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' half-site.
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Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
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D000818:Animals; D019556:COS Cells; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009711:Nucleotides / Q000502:physiology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology; D014162:Transfection
D018031:Connexin 43; D018076:DNA, Complementary; D007202:Indicators and Reagents; D009711:Nucleotides; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones