Negative regulation of the glycoprotein hormone α gene promoter by thyroid hormone : mutagenesis of a proximal receptor binding site preserves transcriptional repression

作者: Laird D. Madison , James A.O. Ahlquist , Selwyn D. Rogers , J.Larry Jameson

DOI: 10.1016/0303-7207(93)90060-W

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摘要: Abstract Transcription of the glycoprotein hormone α gene is repressed by thyroid receptor (TR) in a dependent manner. Previous studies identified TR binding site immediately downstream TATA box. Site directed mutagenesis and transient expression were used to evaluate role this as negative response element (nTRE). Mutagenesis putative (nTRE) eliminated but failed eliminate regulation T3. A mutation which converted nTRE higher affinity palindromic did not enhance repression, rather regulation. Proximal promoter sequences between −100 + 44 replaced with heterologous thymidine kinase resulting construct that was T3 treatment. This finding confirmed repression required proximal also indicated occur interference function upstream enhancers. These indicate adjacent box for mediated suggest may involve protein-protein interactions promoter-specific transcription factors.

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