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（由申请方提供）：真核DNA包装在染色质中，该染色质具有明确的组织。染色质由核小体构建块组成，其沿DNA的沿着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。核小体通过许多机制被高度调节，包括：翻译后修饰、由分子伴侣促进的沉积和驱逐，以及由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控蛋白相互作用进一步调控基因表达。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节至关重要。在这里，我们建议，以进一步我们的理解，这个接口，首先映射的基因组位置的个别核小体国家在高分辨率的模型基因表达程序（热休克和孢子形成）展开。核小体状态的实例包括组蛋白修饰和核小体定相、定位和宽度。第二，我们将确定这些国家的贡献，染色质组织和基因表达，通过检查未能发生什么时，这些国家通过诱变消除。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核小体的高分辨率全基因组图谱。这些目标的目的是首先描述景观的核小体状态在高分辨率下，然后确定它们的功能，然后确定它们的相互作用与基因调控因子主要使用酵母作为一个模型system.Key核小体模式将进一步探讨后生动物模型系统，以确定这些模式是否代表真核生物的基本原则。 公共卫生相关性：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中起着核心作用，并且基因表达是正常和患病细胞行为的起源，因此核小体的基因组组织状态的知识是维持适当细胞生理学和纠正异常状态的关键。这个项目的目的是提供一个更好的理解核小体状态与基因表达。