ROLE OF THE MED1 SUBUNIT OF MEDIATOR CO-ACTIVATOR COMPLEX IN NEURAL STEM CELLS

介导共激活复合物的 MED1 亚基在神经干细胞中的作用

• 批准号: 8282246
• 负责人: DAVID I GOTTLIEB
• 金额: $ 7.6万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8282246
• 关键词: Affect; Antibodies; Apoptosis; Astrocytes; Binding; Biological; Biological Assay; Biological Process; Brain; Bromodeoxyuridine; Cell Culture Techniques; Cell division; Cell physiology; Cells; Cerebral cortex; Clinical; Complex; Corpus striatum structure; DNA; Development; Diagnosis; Disease; Enhancers; Eukaryotic Cell; Family; Feasibility Studies; Fetus; Fibroblasts; Future; Genes; Genetic Transcription; Goals; Grant; Hereditary Disease; Hippocampus (Brain); Histology; Histone H3; Human; Individual; Investigation; Knock-out; Knockout Mice; Knowledge; Lead; Life; Liver; Maps; Mediator of activation protein; Modeling; Morphology; Mus; Muscle; Mutate; Mutation; Neural tube; Neuroglia; Neurons; Newborn Infant; Oligodendroglia; Pilot Projects; Play; Population; Process; Production; Prosencephalon; Proteins; Publishing; RNA Polymerase II; Regulatory Pathway; Research Design; Resources; Role; Signal Transduction; Staging; Staining method; Stains; Stem cells; System; TdT-Mediated dUTP Nick End Labeling Assay; Testing; Time; Tissues; Wit; Work; base; brain cell; caspase-3; cell killing; cell type; developmental disease; in vivo; interest; malformation; nerve stem cell; nestin protein; novel; programs; promoter; protein complex; pup; recombinase; relating to nervous system; research study; tissue culture; transcription factor; translational neuroscience

DESCRIPTION (provided by applicant): The Mediator Co-activator Complex (Mediator) is a 25-30 protein complex that plays a pivotal role in regulating gene transcription in eukaryotic cells. Mediator is expressed in brain cells but currently its precise functions have not been defined. In particular we lack of understanding of the roles of Mediator subunits that interact wit neural transcription factors. In this pilot project we'll investigate the function of the Mediator1 subunit (Med1) in neural stem cells using conditional Med1 knockout mice. We will determine if neural stem cells survive in absence of Med1. We will also use a combination of in vivo and cell culture analyses to define the basic biological processes that are perturbed by lack of Med1. These experiments will give a first look at the role of Med1 in neural stem cells and provide a framework for future large-scale studies of this and other Mediator subunits. Gene transcription is a fundamental aspect of neural cell life and Mediator is likely to be an integral part of it. A number of human neural genetic disorders arise from mutation of Mediator subunits so this work is highly relevant to clinical and translational neuroscience. PUBLIC HEALTH RELEVANCE: This project investigates a complex of 30 proteins that is essential for transcription of most genes in humans. Three of the proteins are mutated to give serious developmental disorders in humans including severe malformations of the neural tube and brain. Very little is known about the complex in neural stem cells, neurons and glia so the results will likely be relevant to understanding neural diseases and in their diagnosis and treatment.

描述（由申请人提供）：Mediator Co-activator Complex （Mediator）是一种25-30蛋白复合物，在真核细胞中调节基因转录起关键作用。中介体在脑细胞中表达，但其确切功能目前尚未明确。特别是我们缺乏与神经转录因子相互作用的中介亚单位的作用的理解。在这个试验项目中，我们将研究Mediator1的功能