The chromatin architecture of a promoter is an important determinant of its transcriptional response. For most target genes, the thyroid hormone receptor (TR) activates gene expression in response to thyroid hormone (T 3 ). In contrast, the thyroid-stimulating hormone ␣-subunit (TSH␣) gene promoter is down-regulated by TR in the presence of T 3 . Here we utilize the capacity for the Xenopus oocyte to chromatinize exogenous nuclearinjected DNA to analyze the chromatin architecture of the TSH␣

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... moter and how this changes upon TR-mediated regulation. Interestingly, in the oocyte, the TSH␣ promoter was positively regulated by T 3 . In the inactive state, the promoter contained six loosely positioned nucleosomes. The addition of TR/retinoid X receptor together had no effect on the chromatin structure, but the inclusion of T 3 induced strong positioning of a dinucleosome in the TSH␣ proximal promoter that was bordered by regions that were hypersensitive to cleavage by methidiumpropyl EDTA. We identified a novel thyroid response element that coincided with the proximal hypersensitive region. Furthermore, we examined the consequences of mutations in TR that impaired coactivator recruitment. In a comparison with the Xenopus TR␤A promoter, we found that the effects of these mutations on transactivation and chromatin remodeling were significantly more severe on the TSH␣ promoter.