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首页> 外文期刊>Molecular and Cellular Biology >Nuclear Receptor Corepressor Recruitment by Unliganded Thyroid Hormone Receptor in Gene Repression during Xenopus laevis Development
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Nuclear Receptor Corepressor Recruitment by Unliganded Thyroid Hormone Receptor in Gene Repression during Xenopus laevis Development

机译：非洲爪蟾发育过程中未配体甲状腺激素受体在基因抑制中的核受体共募集。

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Thyroid hormone receptors (TR) act as activators of transcription in the presence of the thyroid hormone (T3) and as repressors in its absence. While many in vitro approaches have been used to study the molecular mechanisms of TR action, their physiological relevance has not been addressed. Here we investigate how TR regulates gene expression during vertebrate postembryonic development by using T3-dependent amphibian metamorphosis as a model. Earlier studies suggest that TR acts as a repressor during premetamorphosis when T3 is absent. We hypothesize that corepressor complexes containing the nuclear receptor corepressor (N-CoR) are key factors in this TR-dependent gene repression, which is important for premetamorphic tadpole growth. To test this hypothesis, we isolated Xenopus laevis N-CoR (xN-CoR) and showed that it was present in pre- and metamorphic tadpoles. Using a chromatin immunoprecipitation assay, we demonstrated that xN-CoR was recruited to the promoters of T3 response genes during premetamorphosis and released upon T3 treatment, accompanied by a local increase in histone acetylation. Furthermore, overexpression of a dominant-negative N-CoR in tadpole tail muscle led to increased transcription from a T3-dependent promoter. Our data indicate that N-CoR is recruited by unliganded TR to repress target gene expression during premetamorphic animal growth, an important process that prepares the tadpole for metamorphosis.
机译：甲状腺激素受体（TR）在存在甲状腺激素（T 3 ）时起转录激活剂的作用，在不存在时起抑制作用。尽管许多体外方法已用于研究TR作用的分子机制，但尚未解决它们的生理相关性。在这里，我们通过使用T 3 依赖的两栖类变态作为模型，研究TR如何在脊椎动物胚胎后发育过程中调节基因表达。较早的研究表明，当不存在T 3 时，TR可以在变态前发挥抑制作用。我们假设包含核受体corepressor（N-CoR）的corepressor复合物是这种TR依赖的基因阻遏的关键因素，这对于变质前t的生长很重要。为了验证这一假设，我们分离了非洲爪蟾（Nano-CoR）（xN-CoR）并显示它存在于前t和变态t中。使用染色质免疫沉淀试验，我们证明了xN-CoR在变态前期被募集到T 3 反应基因的启动子，并在T 3 处理后释放，并伴随局部增加在组蛋白乙酰化中。此外，t尾肌中显性负性N-CoR的过量表达导致T 3 依赖启动子的转录增加。我们的数据表明，N-CoR由未配体TR募集，以在变态前动物的生长过程中抑制靶基因的表达，这是为the变态做准备的重要过程。

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