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：
8612654
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/8612654
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 Histones Individual Intestines Location Maps Methods Molecular Conformation 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 cohesin deep sequencing developmental disease genome-wide histone modification in vivo in vivo Model innovation novel piRNA public health relevance research study segregation tool transcription factor transcription factor TFIIIC

项目摘要

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.

三维基因组组织，其中线性DNA序列分为功能上不同的域，对于每个单元格中的遗传信息的精确部署至关重要类型。最近，越来越多的破坏性疾病和疾病归因于基因组组织的破坏，但机械基础的理解仍然很少，特别是体内。特别是，如何将结合因子和序列元素的活性转化为表观遗传态和三维基因组结构域控制基因表达神秘。秀丽隐杆线虫提供了一个实验上有利的体内模型，以剖析控制基因组域的适当建立的机制。手头的数据指向小说序列特异性因子（SNAP190）与RNA成分起作用的机制聚合酶III复合物，以定义一个大型基因组结构域，该结构域具有组织特异性，协调的调节数千个非编码小RNA。在此提案中，强大的遗传和基因组秀丽隐杆线虫的工具将用于研究SNAP190，RNA聚合酶III，粘着蛋白和其他候选因素，与染色质状态相互作用（AIM 1），染色体环（AIM 2）和顺式 - 元素（目标3）来定义和调节基因表达的边界，并调节这种独特的基因组领域。拟议的实验的成功完成将阐明尚未理解的在体内驱动大规模基因组组织的至关重要的机制。