Nuclear Receptor Coregulator Functional Pathology in Metabolic Disease

NRs通过与辅调节因子相互作用发挥作用，包括N-COR和SMRT等相互作用的辅阻遏子 与未连接的NRs，以及与连接的NRs相互作用的辅阻遏子，如RIP140。辅抑制子， 反过来，将组蛋白脱乙酰酶(HDAC)招募到NR结合的靶基因上。在这里，我们建议确定 协同调节因子在代谢病理性影响细胞基因表达调控中的作用 疾病，即脂肪细胞和肝脏。具体地说，该项目建议生成和验证 辅调节基因敲除试剂在脂肪细胞和小鼠肝脏中的作用程度和 整合辅阻遏子对脂肪细胞基因表达的调节，并确定其程度和 辅阻遏子对小鼠肝脏基因表达调控的整合。

NRs function by interacting with coregulators, including corepressors such as N-CoR and SMRT that interact with unliganded NRs, and corepressors such as RIP140 that interact with liganded NRs. The corepressors, in turn, recruit histone deacetylase (HDAC) to the NR-bound target genes. Here we propose to determine the role of coregulators in regulating gene expression in cells that are pathologically affected in metabolic disease, namely adipocytes and liver. Specifically, this project proposes the generation and validation of coregulator knockdown reagents in adipocytes and mouse liver, the determination of the extent and integration of corepressor regulation of gene expression in adipocytes, and determining the extent and integration of corepressor regulation of gene expression in mouse liver.