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Movement of regulated genes to the nuclear periphery

受调控基因向核外围的运动

基本信息

批准号：
7516086
负责人：
GEORGE M SANTANGELO
金额：
$ 3.29万
依托单位：
UNIVERSITY OF SOUTHERN MISSISSIPPI
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7516086
关键词：
Animal Model Arts Authorship Biochemical Biochemistry Biological Biological Assay Biological Models Cell Nucleolus Cell Nucleus Cell membrane Cells Chromatin Chromosomes Cloning Complex Congenital Disorders Development Dissection Environment Enzymes Eukaryota Eukaryotic Cell Experimental Designs Facility Construction Funding Category Figs - dietary Follow-Up Studies Galactose Gene Expression Gene Expression Regulation Genes Genetic Genetic Engineering Genetic Recombination Genetic Transcription Genotype Glucose Goals Green Fluorescent Proteins Image Individual Knock-out Learning Left Localized Location Malignant Neoplasms Microscope Modeling Molecular Biology Monitor Movement Neurodegenerative Disorders Nitrogen Nitrogen Fixation Genes Northern Blotting Nuclear Nuclear Pore Complex Organism Paper Philosophy Polymerase Chain Reaction Positioning Attribute Procedures Production Property Proteins Public Health Publishing Reagent Reporter Reporting Repression Research Research Personnel Saccharomyces cerevisiae Spottings Standards of Weights and Measures Students System Technical Expertise Techniques Therapeutic Training Tube Type 7 Spinocerebellar Ataxia Week Work Yeasts base experience human disease plasmid DNA promoter research and development single cell analysis

项目摘要

DESCRIPTION (provided by applicant): The long term objective of this project is to understand the relationship between the regulation of gene expression and nuclear substructure. Recent reports indicate that, soon after they are transcriptionally induced, genes in the model eukaryote Saccharomyces cerevisiae move to the nuclear periphery and associate with nuclear pore complexes. Specific Aim 1 is to use a single cell assay for regulated gene expression to determine the relationship between perinuclear gene anchoring and the ON and OFF transcriptional states. Specific Aim 2 is to explore the possibility that movement to the nuclear periphery is a universal property of transcriptionally induced genes. If not it will be important to determine whether transcriptionally active genes not anchored at the nuclear periphery become anchored elsewhere in the nucleus, for example within the nucleolus. Understanding these and other related aspects of gene regulation is key to the development of effective therapeutics for human diseases, since improperly regulated transcription is often responsible for congenital disorders and cancer. For example, the neurodegenerative disease spinocerebellar ataxia 7 results from a trinucleotide expansion in the SCA7 subunit of the chromatin modifying TFTC complex. These studies will take advantage of the integrated approach, including genetic, cell biological, and biochemical analyses, that is possible in the S. cerevisiae model system. The ease with which this organism can be grown and manipulated also makes it an ideal choice in providing research opportunities for undergraduate students. PUBLIC HEALTH RELEVANCE: The long-term objective of this project is to understand the relationship between the regulation of gene expression and nuclear substructure. Understanding these and related aspects of gene regulation is key to the development of effective therapeutics for human diseases, since improperly regulated transcription is often responsible for congenital disorders and cancer.

项目描述（申请人提供）：本项目的长期目标是了解基因表达调控与核亚结构之间的关系。最近的报道表明，在转录诱导后不久，真核生物酿酒酵母模型中的基因移动到核周边并与核孔复合物相关联。具体目标1是使用单细胞测定调节基因表达，以确定核周基因锚定和ON和OFF转录状态之间的关系。具体目标2是探索的可能性，运动到核周边是转录诱导基因的普遍属性。如果不是，则确定没有锚定在核外围的转录活性基因是否锚定在核的其他地方，例如核仁内，将是重要的。了解基因调控的这些和其他相关方面是开发人类疾病有效治疗方法的关键，因为转录调控不当通常是先天性疾病和癌症的原因。例如，神经变性疾病脊髓小脑共济失调7由染色质修饰TFTC复合物的SCA7亚基中的三核苷酸扩增引起。这些研究将利用综合方法，包括遗传学，细胞生物学和生化分析，这是可能的，在S。酿酒酵母模型系统。这种有机体可以轻松生长和操纵，也使其成为为本科生提供研究机会的理想选择。公共卫生相关性：该项目的长期目标是了解基因表达调控与核亚结构之间的关系。了解基因调控的这些和相关方面是开发人类疾病有效治疗方法的关键，因为转录调控不当通常是先天性疾病和癌症的原因。