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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

基本信息

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
项目类别：
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

项目摘要

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.

NR通过与辅调节因子相互作用发挥功能，包括辅抑制因子，如N-CoR和SMRT，与配体化的NR和辅阻遏物如与配体化的NR相互作用的RIP 140。辅阻遏物，进而将组蛋白脱乙酰酶（HDAC）募集至NR结合的靶基因。在这里，我们建议确定辅调节因子在调节代谢紊乱的病理性影响细胞中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在脂肪细胞和小鼠肝脏中的辅调节因子敲低试剂，整合脂肪细胞中基因表达的辅阻遏物调节，并确定其程度和小鼠肝脏中基因表达辅阻遏物调控的整合