Metamorphic T3-response genes have specific co-regulator requirements

Thyroid hormone receptors (TRs) have several regulatory functions in vertebrates. In the absence of thyroid hormone (T-3; triiodothyronine), apo-TRs associate with co-repressors to repress transcription, whereas in the presence of T-3, holo-TRs engage transcriptional coactivators. Although many studies have addressed the molecular mechanisms of T-3 action, it is not known how specific physiological responses arise. We used T-3-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 tadpoles, we found that TRs are physically associated with T-3-responsive promoters, whether or not T-3 is present. Addition of T-3 results in histone H4 acetylation specifically on T-3-response genes. Most importantly, we show that individual T-3-response genes have distinct co-regulator requirements, the T-3-dependent co-repressor-to-coactivator switch being gene-specific for both co-regulator categories.