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Deciphering mechanisms governing functional partitioning of the C. elegans genome

破译控制线虫基因组功能分区的机制

基本信息

批准号：
9000710
负责人：
VALERIE J REINKE
金额：
$ 31.64万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9000710
关键词：
Address Affect Architecture Automobile Driving Beryllium Binding Binding Sites Bruck-de Lange syndrome C. elegans genome CCCTC-binding factor Caenorhabditis elegans Cell Nucleus Cells ChIP-seq Chromatin Chromatin Loop Chromosomes Code Complex DNA Sequence Data Development Disease Electron Transport Complex III Elements Environment Enzymes Epigenetic Process Event Exhibits Gene Expression Genes Genetic Genome Genomics Germ Cells Germ Lines Hand Health Histones Individual Intestines Location Maps Methods Mutate Organism Pattern Polymerase Property RNA Polymerase II RNA Polymerase III Regulation Roberts-SC phocomelia syndrome Signal Transduction Site Small RNA Specificity Techniques Tissue-Specific Gene Expression Tissues Translating Triad Acrylic Resin Untranslated RNA Work base cell type chromatin immunoprecipitation chromatin modification chromosome conformation capture cohesin deep sequencing developmental disease genetic information genome-wide genomic tools histone modification in vivo in vivo Model innovation novel piRNA research study segregation transcription factor transcription factor TFIIIC

项目摘要

DESCRIPTION (provided by applicant): Three-dimensional genome organization, in which the linear DNA sequence is partitioned into functionally distinct domains, is essential for the precise deployment of genetic information in every cell type. An increasing number of devastating disorders and diseases have recently been attributed to disruption of genome organization, yet the mechanistic underpinnings remain poorly understood, especially in vivo. In particular, how the activity of binding factors and sequence elements is translated to epigenetic states and three-dimensional genomic domains to govern gene expression remains mysterious. C. elegans provides an experimentally advantageous in vivo model to dissect the mechanisms governing proper establishment of genomic domains. Data in hand points to a novel mechanism in which a sequence-specific factor (SNAP190) acts with components of the RNA polymerase III complex to define a large genomic domain exhibiting tissue-specific, coordinated regulation of thousands of noncoding small RNAs. In this proposal, the powerful genetic and genomic tools of C. elegans will be employed to investigate how SNAP190, RNA polymerase III, cohesin, and other candidate factors, interact with chromatin states (Aim 1), chromosomal looping (Aim 2), and cis- elements (Aim 3) to define the boundaries of, and regulate gene expression within, this unique genomic domain. The successful completion of the proposed experiments will illuminate the poorly understood yet vitally important mechanisms driving large-scale genome organization in vivo.

描述（由申请人提供）：