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Determinants of chromatin disruption and transcriptional regulation instigated by the thyroid hormone receptor: hormone‐regulated chromatin disruption is not sufficient for transcriptional activation
Author(s) -
Wong Jiemin,
Shi YunBo,
Wolffe Alan P.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.11.3158
Subject(s) - biology , chromatin , thyroid hormone receptor , hormone , thyroid , microbiology and biotechnology , hormone receptor , transcriptional regulation , thyroid hormone receptor beta , nuclear receptor , chia pet , receptor , chromatin remodeling , genetics , transcription factor , endocrinology , gene , cancer , breast cancer
Chromatin disruption and transcriptional activation are both thyroid hormone‐dependent processes regulated by the heterodimer of thyroid hormone receptor and 9‐ cis retinoic acid receptor (TR–RXR). In the absence of hormone, TR–RXR binds to nucleosomal DNA, locally disrupts histone–DNA contacts and generates a DNase I‐hypersensitive site. Chromatin‐bound unliganded TR–RXR silences transcription of the Xenopus TRβA gene within a canonical nucleosomal array. On addition of hormone, the receptor directs the extensive further disruption of chromatin structure over several hundred base pairs of DNA and activates transcription. We define a domain of the TR protein necessary for directing this extensive hormone‐dependent chromatin disruption. Particular TR–RXR heterodimers containing mutations in this domain are able to bind both hormone and their thyroid hormone receptor recognition element (TRE) within chromatin, yet are unable to direct the extensive hormone‐dependent disruption of chromatin or to activate transcription. We distinguish the hormone‐dependent disruption of chromatin and transcriptional activation as independently regulated events through the mutagenesis of basal promoter elements and by altering the position and number of TREs within the TRβA promoter. Chromatin disruption alone on a minichromosome is shown to be insufficient for transcriptional activation of the TRβA gene.