Metamorphic T3-response genes have specific co-regulator requirements
Metamorphic T3-response genes have specific co-regulator requirements
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DOI：
10.1038/sj.embor.embor908
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发表时间：
2003-09-01
期刊：
影响因子：
7.7
通讯作者：
Demeneix, BA
中科院分区：
文献类型：
--
作者：
Havis, E;Sachs, LM;Demeneix, BA
甲状腺激素受体（TRs）在脊椎动物中具有多种调节功能。在没有甲状腺激素（T-3;三碘甲状腺原氨酸）的情况下，apo-TRs与辅阻遏物结合以抑制转录，而在T-3存在的情况下，holo-TRs参与转录辅激活因子。虽然许多研究已经解决了T-3作用的分子机制，但尚不清楚具体的生理反应如何产生。我们使用T-3依赖的两栖动物变态来分析TRs如何与特定的共调节因子相互作用，以差异调节发育过程中的基因表达。使用染色质免疫沉淀研究组织从前变质蝌蚪，我们发现，TRs物理与T-3响应启动子，无论T-3是否存在。添加T-3导致组蛋白H4乙酰化，特异性地作用于T-3反应基因。最重要的是，我们表明，个别的T-3反应基因有不同的共调节要求，T-3依赖的共阻遏物，共激活开关是基因特异性的两个共调节类别。
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.