High Resolution Mapping of Function Elements in the Yeast Genome

酵母基因组功能元件的高分辨率图谱

• 批准号: 8293295
• 负责人: B FRANKLIN PUGH
• 金额: $ 34.65万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-26 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8293295
• 关键词: Address; Antibodies; Behavior; Binding; Biological Assay; Biological Models; Biology; Cell physiology; Cells; Chromatin; Chromatin Remodeling Factor; DNA; Data Analyses; Deposition; Development; Disease; Drosophila genome; Enzymes; Eukaryota; Formaldehyde; Funding; Fungal Genome; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genome; Genomics; Goals; Health; Heat-Shock Response; Histones; Human; Indium; Individual; Knowledge; Lead; Link; Location; Maps; Measurable; Medical; Modeling; Modification; Molecular Chaperones; Mutagenesis; Mutate; Nature; Nomenclature; Nuclear; Nucleosome Core Particle; Nucleosomes; Nutrient; Pattern; Phase; Play; Positioning Attribute; Post-Translational Protein Processing; Procedures; Protein Binding; Publishing; RNA Polymerase II; Regulation; Regulator Genes; Regulatory Element; Relative (related person); Research; Resolution; Role; Saccharomyces; Saccharomyces cerevisiae; Saccharomycetales; Site; Starvation; Technology; Time; Width; Work; Yeasts; base; genetic regulatory protein; genome-wide; histone modification; in vivo; insight; man; pluripotency; programs; protein crosslink; public health relevance; response

DESCRIPTION (provided by applicant): Eukaryotic DNA is packaged into chromatin, and this chromatin has a well-defined organization. Chromatin is composed of nucleosome building blocks, whose positioning along the DNA dictates the accessibility of gene regulatory elements, and ultimately the expression levels of genes. Nucleosomes are highly regulated through many mechanisms including: post-translational modifications, deposition and eviction that is facilitated by chaperones, and re-positioning facilitated by chromatin remodeling complexes. Such nucleosome states further regulate gene expression by interacting with specific gene regulatory proteins. How nucleosome states interface with gene regulatory factors is largely unknown and is central to our understanding of how gene expression is controlled and mis-regulated in diseases. Here, we propose to further our understanding of this interface by first mapping the genomic position of individual nucleosome states at high resolution as model gene expression programs (heat shock and sporulation) unfold. Examples of nucleosome states include histone modifications, and nucleosome phasing, positioning, and width. Second, we will ascertain the contribution of such states to chromatin organization and gene expression, by examining what fails to happen when such states are eliminated through mutagenesis. Third, we will create high-resolution genome-wide maps of nucleosomes that interact with specific chromatin and gene regulatory factors. These aims are intended to first describe the landscape of nucleosomal states at high resolution, then identify their function, and then ascertain their interplay with gene regulatory factors using primarily Saccharomyces as a model system.Key nucleosomal patterns will be further explored in metazoan model systems, to ascertain whether such patterns represent fundamental principles in eukaryotes. PUBLIC HEALTH RELEVANCE: Since nucleosome positioning and regulation play central roles in controlling gene expression from yeast to man, and gene expression is the origin of both normal and diseased cellular behavior, knowledge of the genomic organizational state of nucleosomes is key toward maintaining proper cell physiology and rectifying aberrant states. This project is intended to provide a greater understanding of nucleosomal states in relation to gene expression.

描述（申请人提供）：真核DNA被包装到染色质中，并且该染色质具有明确的组织。染色质由核小体构件组成，其沿 DNA 的定位决定了基因调控元件的可及性，并最终决定了基因的表达水平。核小体通过多种机制受到高度调控，包括：翻译后修饰、分子伴侣促进的沉积和驱逐，以及染色质重塑复合物促进的重新定位。这种核小体状态通过与特定基因调节蛋白相互作用进一步调节基因表达。核小体状态如何与基因调控因子相互作用在很大程度上是未知的，并且对于我们理解疾病中基因表达如何被控制和错误调控至关重要。在这里，我们建议首先随着模型基因表达程序（热休克和孢子形成）的展开，以高分辨率绘制单个核小体状态的基因组位置，以进一步了解该界面。核小体状态的例子包括组蛋白修饰、核小体定相、定位和宽度。其次，我们将通过检查通过诱变消除这些状态时不会发生的情况来确定这些状态对染色质组织和基因表达的贡献。第三，我们将创建与特定染色质和基因调控因子相互作用的高分辨率全基因组核小体图谱。这些目标旨在首先以高分辨率描述核小体状态的景观，然后识别它们的功能，然后主要使用酵母菌作为模型系统来确定它们与基因调控因子的相互作用。关键核小体模式将在后生动物模型系统中进一步探索，以确定这些模式是否代表真核生物的基本原理。 公共健康相关性：由于核小体的定位和调节在控制从酵母到人类的基因表达方面发挥着核心作用，而基因表达是正常和患病细胞行为的起源，因此了解核小体的基因组组织状态是维持适当的细胞生理学的关键并纠正异常状态。该项目旨在更好地了解与基因表达相关的核小体状态。