Metamorphic T3‐response genes have specific co‐regulator requirements

• DOI: 10.1038/sj.embor.embor908
• Publication Date: 2003-08-29T13:55:43Z
• Authors: Emmanuelle Havis; Laurent M Sachs; Barbara A Demeneix
• Keywords: YY1; Thyroid hormone receptor

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.