Odorant Receptor Gene Regulation

气味受体基因调控

• 批准号: 8701631
• 负责人: Timothy S McClintock
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2016-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8701631
• 关键词: Afferent Neurons; Alleles; Back; Binding; Cells; Chemicals; Chromatin; Code; Complex; Data; Development; Discrimination; Disease; Enhancers; Equilibrium; Event; Family; Feedback; Future; Gene Expression; Gene Expression Regulation; Gene Family; Genes; Genetic Predisposition to Disease; Genetic Transcription; Histones; In Vitro; Mammals; Modeling; Modification; Molecular; Mus; Mutant Strains Mice; Mutation; Neurons; Odorant Receptors; Odors; Olfactory Nerve; Outcome; Process; Property; Receptor Gene; Recruitment Activity; Reporter Genes; Repression; Role; Site; Specificity; Testing; Transcription Initiation; Work; afferent nerve; base; cancer genetics; chromatin modification; coping; emx2 protein; genetic discrimination; homeodomain; in vivo; interest; neuron development; promoter; public health relevance; receptor expression; selective expression; transcription factor

DESCRIPTION (provided by applicant): This project investigates the actions of two homeodomain transcription factors that help control expression of nearly all of the more than 1,000 mouse odorant receptor genes, expression so finely regulated that each olfactory nerve cell expresses just one allele of one odorant receptor gene. The overarching hypothesis for the project proposes that homeodomain transcription factor stimulation of odorant receptor gene transcription triggers local positive feedback acting through active chromatin modifications while simultaneously enhancing global negative feedback acting through repressive chromatin modifications, competing events capable of explaining the singularity of odorant receptor expression. This project tests whether the transcription factors act directly at promoters and enhancers of odorant receptor genes, and whether these events are associated with selected active chromatin modifications at odorant receptor genes.

描述(申请人提供)：这个项目研究两个同源结构域转录因子的作用，它们帮助控制几乎所有1000多个小鼠气味受体基因的表达，表达受到如此精细的调控，以至于每个嗅神经细胞只表达一个气味受体基因的一个等位基因。该项目的总体假设是，同源结构域转录因子刺激气味受体基因转录，通过主动染色质修饰触发局部正反馈作用，同时通过抑制性染色质修饰增强全局负反馈作用，这些竞争事件能够解释气味受体表达的奇异性。该项目测试转录因子是否直接作用于气味受体基因的启动子和增强子，以及这些事件是否与气味受体基因上选定的活性染色质修饰有关。