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High Resolution Mapping of Functional Elements in the Yeast Genome

酵母基因组功能元件的高分辨率图谱

基本信息

批准号：
10357973
负责人：
B FRANKLIN PUGH
金额：
$ 40.07万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-11 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10357973
关键词：
Address Architecture Binding Biochemical Biological Models Biology Cell Differentiation process Cells ChIP-seq Chromatin Chromatin Remodeling Factor Complex CpG Islands Crude Extracts DNA DNA Sequence Diffuse Disease ENG gene Elements Functional disorder Funding Gene Expression Regulation Genes Genetic Transcription Genome Genomics Goals Health Histones Human In Vitro Individual Medical Methods Modeling Molecular Chaperones Nuclear Nucleosomes Pattern Physiological Play Positioning Attribute Proteins Regulation Regulator Genes Research Resolution Role Saccharomyces cerevisiae Saccharomycetales Shapes Site Specific qualifier value Structure System Testing Transcriptional Regulation Validation Work Yeasts cell behavior cell type chromatin remodeling complex biological systems embryonic stem cell epigenome experimental study genome-wide human DNA in vivo novel particle pluripotency promoter reconstitution yeast genome

项目摘要

The budding yeast Saccharomyces cerevisiae is used as model system to understand genomic mechanisms by which chromatin organization is established. The start sites of genes, or promoters, are typically encased in a nucleosome-free region, that is bookended with two well-positioned nucleosomes. This precise organization is standard for most genes, and plays into how these genes are regulated. Therefore a fundamental understanding of gene regulatory mechanisms requires a complete understanding of how such canonical nucleosome organization arises and guides the placement of the transcription machinery. The proposed work will take advantage of biochemical reconstitution of aspects of canonical nucleosome organization on a genomic scale. This will allow individual mechanistic contributions of chromatin organizing factors and their effectors to be explicitly defined. In particular, how ATP-dependent chromatin remodeler complexes recognize DNA features and sequence-specific organizing factors, will be addressed. The organization of chromatin directs the organized assembly of the transcription machinery. Biochemical reconstitution will be used to tease apart selected individual contributions of chromatin organization and activator/repressor binding towards assembly of the transcription machinery on a genomic scale. Chromatin is generally thought to be composed of nucleosome particles containing 2 copies of each of the four core histones. However, it is now becoming clear that various partially assembled nucleosomes or subnucleosomes exist in vivo, and these structures may play critical roles in chromatin dynamics. The existence of these substructures and the histone chaperones that are likely to be involved in their assembly and disassembly will be investigated on a genomic scale.

以出芽酵母酿酒酵母（Saccharomyces cerevisiae）为模型系统，研究其基因组机制