Nuclear Receptor Coregulator Functional Pathology in Metabolic Disease

代谢性疾病中的核受体共调节功能病理学

• 批准号: 7350615
• 负责人: MITCHELL A. LAZAR
• 金额: $ 28.85万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7350615
• 关键词: ATP-Binding Cassette Transporters; Adipocytes; Adipose tissue; Affect; Atlases; Bioinformatics; Cells; Circadian Rhythms; Class; Collaborations; Communities; Computer software; Cultured Cells; Cytochrome P450; Data; Data Set; Development; Effectiveness; Enzymes; Event; Gene Expression; Gene Expression Regulation; Gene Targeting; Generations; Hepatocyte; Histone Deacetylase; Human; Human Genome; Immunohistochemistry; Individual; Injection of therapeutic agent; Laboratories; Lentivirus Infections; Ligands; Link; Liver; Liver parenchyma; Messenger RNA; Metabolic; Metabolic Diseases; Metabolism; MicroRNAs; Molecular; Mus; NRIP1 gene; Nuclear Receptor Gene; Nuclear Receptors; Numbers; Oligonucleotide Microarrays; Pathology; Pathway Analysis; Pathway interactions; Pharmaceutical Preparations; Physiology; Preparation; Proteins; Publishing; Reagent; Recruitment Activity; Regulation; Repression; Resources; Role; Subfamily lentivirinae; Tail; Testing; Time; Tissues; Validation; Veins; Vertebral column; Whole Organism; Work; human NCOR1 protein; in vivo; insight; novel; nuclear receptor coactivator 1; receptor; receptor binding; small hairpin RNA

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.

NRS函数通过与核心调节剂相互作用，包括相互作用的N-COR和SMRT等核心压力器 使用非配体的NR和与配体NRS相互作用的RIP140等核心压力器。核心器， 反过来，募集组蛋白脱乙酰基酶（HDAC）到NR结合的靶基因。在这里我们建议确定 核心节剂在调节基因表达中的作用 疾病，即脂肪细胞和肝脏。具体而言，该项目提出了生成和验证 脂肪细胞和小鼠肝脏中的cOREGULATOR敲低试剂，确定程度和 整合脂肪细胞中基因表达的核心压缩，并确定程度和程度 小鼠肝脏基因表达的核心压缩的整合。