Thyroid Hormone Receptor Corepressors: Requirements and Selectivity for Histone Modifications Cell Culture

甲状腺激素(T3)是神经元分化和成熟的重要调节因子。甲状腺激素受体(Trr)是一种配体调节的转录因子，调节基因的抑制和激活。已经描述了许多不同的辅抑制子与tr相互作用。辅阻遏物以激素敏感、激素非依赖或激素依赖的方式与受体结合。然而，目前还不清楚单个辅阻遏子在tr介导的基因抑制和激活以及tr介导的神经元分化和成熟中发挥了哪些生物学功能。本项目通过组蛋白修饰(乙酰化、甲基化、磷酸化和泛素化)分析辅抑制子在染色质背景下的选择性和特异性，以及辅抑制子对神经元分化和成熟的影响。

Thyroid hormone (T3) is an important regulator of neuronal differentiation and maturation. The receptor for thyroid hormone (TR) is a ligand regulated transcription factor mediating both gene repression and activation. A number of different corepressors have been described to interact with TR. Corepressors bind either in a hormone-sensitive, hormone-independent or hormone-dependent manner to TR. However, it is not understood which biological functions individual corepressors play in the context of TR-mediat ed gene repression and activation as well as for TR-mediated neuronal differentiation and maturation. This project analyses the selectivity and specificity of corepressors in the context of chromatin through histone modifications (acetylation, methylation, phosphorylation and ubiquitinylation) of TR target genes as well as the impact of corepressors on neuronal differentiation and maturation.