Chromatin Remodeling by the Thyroid Hormone Receptor in Regulation of the Thyroid-stimulating Hormone α-Subunit Promoter

Trevor N. Collingwood, Fyodor D. Urnov, V. Krishna K. Chatterjee, Alan P. Wolffe
2001 Journal of Biological Chemistry  
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␣
more » ... 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.
doi:10.1074/jbc.m105172200 pmid:11454868 fatcat:mhq5sptnkngp5kpufdlh4ebp7e