Havis Emmanuelle, Sachs Laurent M, Demeneix Barbara A
Département Régulations, Développement et Diversité Moléculaire, UMR-5166 CNRS, 7 Rue Cuvier, 75231 Paris Cedex 05, France.
EMBO Rep. 2003 Sep;4(9):883-8. doi: 10.1038/sj.embor.embor908. Epub 2003 Aug 15.
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.
甲状腺激素受体（TRs）在脊椎动物中具有多种调节功能。在缺乏甲状腺激素（T3；三碘甲状腺原氨酸）的情况下，无激素TRs与共抑制因子结合以抑制转录，而在T3存在时，有激素TRs与转录共激活因子结合。尽管许多研究探讨了T3作用的分子机制，但尚不清楚特定的生理反应是如何产生的。我们利用依赖T3的两栖类变态来分析TRs如何与特定的共调节因子相互作用，从而在发育过程中差异调节基因表达。通过染色质免疫沉淀研究变态前蝌蚪的组织，我们发现无论T3是否存在，TRs都与T3反应性启动子物理结合。添加T3会导致组蛋白H4仅在T3反应基因上发生乙酰化。最重要的是，我们表明单个T3反应基因具有不同的共调节因子需求，T3依赖的共抑制因子到共激活因子的转换对于这两类共调节因子都是基因特异性的。
