C. elegans transcriptional regulatory elements

线虫转录调控元件

基本信息

批准号：
8460166
负责人：
PAUL Warren STERNBERG
金额：
$ 46.82万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8460166
关键词：
Active Sites Algorithms Animal Model Animals Behavior Benchmarking Binding Sites Bioinformatics Biological Biological Assay Caenorhabditis Caenorhabditis elegans Characteristics Computer Simulation Computing Methodologies DNA DNA Sequence Data Development Disease Elements Family Gene Expression Genes Genetic Transcription Genome Genomics Goals Gold Learning Life Cycle Stages Link Maps Measures Methods Modeling Nematoda Output Pattern Phylogenetic Analysis Physiological Physiology Predictive Value Problem Solving Production Property Regulator Genes Regulatory Element Reporter Research Infrastructure Research Personnel Resolution Siblings Site Site-Directed Mutagenesis Small Interfering RNA Source Code Staging System Technology Testing Time Transgenic Animals Transgenic Organisms Validation base cell type chromatin immunoprecipitation cofactor comparative genomics computerized tools gene function genome sequencing genome-wide improved in vivo programs public health relevance research study transcription factor

项目摘要

DESCRIPTION (provided by applicant): Cis-acting regulatory elements control gene expression and are involved in all aspects of development, behavior and physiology; but no cis-regulatory element map yet exists for any metazoan genome. We therefore propose to identify genome-wide cis-regulatory elements in C. elegans. Among existing model organisms, C. elegans offers a strong combination of biological properties, transgenic technology, comparisons to genomes in four sibling species, and critical computational and bioinformatic infrastructure. We intend to find genomic regulatory elements in genes with widely varying expression patterns, gene functions, and cis-element content that drive expression in diverse developmental stages, cell types and physiological conditions. A pipeline of genomic predictions followed by efficient transgenic reporter assays will allow us to generate and analyze 10 DNA constructs each week. In year 1 we plan to identify hundreds of regulatory elements, with higher numbers in following years as we become better at predicting functional elements. Predicted elements will be assigned statistical scores based on the quality of their supporting computational and experimental data. We will also use chromatin immunoprecipitation analyzed by intense sequencing (ChIP-seq) to find regulatory modules, and compare its accuracy in finding functional sequences to that of predictions based on comparative genomics. The first round of our results from direct tests of predicted elements and ChIP-seq will be combined with external data from modENCODE to improve our predictive algorithms for later cycles of genome-wide element prediction. Our data will be released promptly to WormBase, and all our computational tools are freely available with full source code.

描述（申请人提供）：顺式作用调控元件控制基因表达，参与发育、行为和生理学的各个方面；但任何后生动物基因组尚不存在顺式调控元件图谱。因此，我们建议鉴定秀丽隐杆线虫中的全基因组顺式调控元件。在现有的模式生物中，线虫提供了生物特性、转基因技术、与四个兄弟物种的基因组比较以及关键的计算和生物信息学基础设施的强大组合。我们打算在具有广泛不同的表达模式、基因功能和顺式元件含量的基因中找到基因组调控元件，这些元件在不同的发育阶段、细胞类型和生理条件下驱动表达。一系列基因组预测以及高效的转基因报告基因检测将使我们能够每周生成并分析 10 个 DNA 构建体。在第一年，我们计划识别数百个调控元件，随着我们更好地预测功能元件，在接下来的几年中，数量会增加。预测元素将根据其支持计算和实验数据的质量分配统计分数。我们还将使用通过强化测序（ChIP-seq）分析的染色质免疫沉淀来寻找调控模块，并将其寻找功能序列的准确性与基于比较基因组学的预测进行比较。我们对预测元件和 ChIP-seq 的直接测试的第一轮结果将与来自 modENCODE 的外部数据相结合，以改进我们的预测算法，以用于后续全基因组元件预测周期。我们的数据将立即发布到 WormBase，并且我们所有的计算工具都可以免费获得完整的源代码。