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：
8795206
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/8795206
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 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 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）：三维基因组组织，其中线性DNA序列分为功能不同的域，对于每种细胞类型中遗传信息的精确部署至关重要。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，但机械基础仍然知之甚少，尤其是在体内。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域来控制基因表达，这仍然是神秘的。秀丽隐杆线虫提供了一个实验上有利的体内模型，以剖析管理基因组域正确建立的机制。手头的数据指出了一种新的机制，其中序列特异性因子（SNAP190）与RNA聚合酶III复合物的成分作用，以定义一个大型基因组结构域，表现出大型组织特异性的，协调的调节数千个非编码的小RNA。在此提案中，将采用秀丽隐杆线虫的强大遗传和基因组工具来研究SNAP190，RNA聚合酶III，粘蛋白和其他候选因素如何与染色质状态相互作用（AIM 1），染色体循环（AIM 2）（AIM 2）和CIS元素（AIM 3）（AIM 3），以确定基因的范围和调节基因的构成基因的构成，并在此中构成基因的构成。拟议的实验的成功完成将阐明在体内驱动大规模基因组组织的知识较低但至关重要的机制。