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（由申请人提供）：将真核DNA包装成染色质，该染色质具有明确的组织。染色质由核小体组成部分组成，其沿DNA的定位决定了基因调节元件的可及性，最终决定了基因的表达水平。核小组通过许多机制进行了高度调节，包括：伴侣促进的翻译后修饰，沉积和驱逐，以及由染色质重塑复合物促进的重新定位。这样的核小体通过与特定基因调节蛋白相互作用来进一步调节基因表达。核小体状态与基因调节因子的界面在很大程度上是未知的，对于我们对疾病中基因表达的控制和错误调节的理解至关重要。在这里，我们建议通过首先将单个核小体状态的基因组位置作为模型基因表达程序（热休克和孢子形）展开，以进一步了解该界面。核小体状态的例子包括组蛋白的修饰，以及核小体的定位，定位和宽度。其次，我们将通过检查通过诱变消除此类状态时未发生的事情来确定此类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节因子相互作用的核小体的高分辨率全基因组图。这些目标旨在首先以高分辨率描述核小体状态的景观，然后确定其功能，然后确定其与基因调节因子的相互作用，主要使用糖含量为模型系统。键核核体模式将在Metazoan Model Systems中进一步探索，以确定此类模式是否代表Eukarentaltental in eukareartles中的基本原理。 公共卫生相关性：由于核小体定位和调节在控制从酵母到人的基因表达中起着核心作用，而基因表达是正常和患病的细胞行为的起源，因此对核小体基因组组织状态的了解是维持正确细胞生理和循环异常状态的关键。该项目旨在提供与基因表达相关的核小体状态的更多了解。