title: Metamorphic T3-response genes have specific co-regulator requirements.
abstract: Thyroid hormone receptors (TRs) have several regulatory functions in vertebrates. In the absence of thyroid hormone (T3; tri-iodothyronine), 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 immuno-precipitation to study tissue from pre-metamorphic tadpoles, 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.
authors.affiliation: Département Régulations, Développement et Diversité Moléculaire, UMR-5166 CNRS, 7 Rue Cuvier, 75231 Paris Cedex 05, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Havis
authors.forename: Laurent M
authors.initials: LM
authors.lastname: Sachs
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Demeneix
mesh_terms: D000107:Acetylation; D000818:Animals; D006657:Histones / Q000378:metabolism; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D011401:Promoter Regions, Genetic; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D014157:Transcription Factors; D014284:Triiodothyronine