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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
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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.
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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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