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scientific report
EMBO reports 4, 9, 883–888 (2003)
doi:10.1038/sj.embor.embor908
AOP Published online: 15 August 2003

Metamorphic T3-response genes have specific co-regulator requirements

Emmanuelle Havis1, 2, Laurent M. Sachs1, 2 & Barbara A. Demeneix1
1 Département Régulations, Développement et Diversité Moléculaire, USM 501 Muséum National d'Histoire Naturelle, UMR-5166 CNRS, 7 Rue Cuvier, 75231 Paris Cedex 05, France
2 These authors contributed equally to this work


To whom correspondence should be addressed
Laurent M. Sachs Tel: +33 1 40 79 36 04; Fax: +33 1 40 79 36 18; sachs@mnhn.fr


Received 3 February 2003; Accepted 26 June 2003; Published online 15 August 2003.
Abstract

Thyroid hormone receptors (TRs) have several regulatory functions in vertebrates. In the absence of thyroid hormone (T3; triiodothyronine), apo-TRs associate with co-repressors to repress transcription, whereas in the presence of T3, holo-TRs engage transcriptional coactivators. Although many studies have addressed the molecular mechanisms of T3 action, it is not known how specific physiological responses arise. We used T3-dependent amphibian metamorphosis to analyse how TRs interact with particular co-regulators to differentially regulate gene expression during development. Using chromatin immunoprecipitation to study tissue from pre-metamorphic tad-poles, we found that TRs are physically associated with T3-responsive promoters, whether or not T3 is present. Addition of T3 results in histone H4 acetylation specifically on T3-response genes. Most importantly, we show that individual T3-response genes have distinct co-regulator requirements, the T3-dependent co-repressor-to-coactivator switch being gene-specific for both co-regulator categories.

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