Genomic and Functional Analyses of Conserved Noncoding Regions in Vertebrates

脊椎动物保守非编码区域的基因组和功能分析

• 批准号: 7594332
• 负责人: Laura L Elnitski
• 金额: $ 136.68万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7594332
• 关键词: Address; Area; Base Sequence; Binding Sites; Biological; Biological Assay; Characteristics; Class; Collaborations; Diagnostic tests; Elements; Enhancers; Expression Feature; Gene Expression; Gene Expression Regulation; Genome; Genomics; Goals; Human Genome; Indium; Machine Learning; Malignant Neoplasms; Malignant neoplasm of ovary; Methodology; Methylation; Normal tissue morphology; Pathway interactions; Pattern; Promoter Regions; Protein Binding; Research; Site; Structure; Techniques; Testing; Transcriptional Silencer Elements; United States National Institutes of Health; Vertebrates; Work; base; bisulfite; comparative; follow-up; functional genomics; high throughput screening; insight; member; network models; novel; promoter; transcription factor; vertebrate genome

The major aims of the Genomic Functional Analysis Section are to identify cis-and trans-acting functional elements in vertebrate genomes. Approaches to find these elements incorporate computational and experimental components including whole-genome comparative analyses, predictions based on machine learning techniques and experimental testing. Major focus areas include identifying bidirectional promoters in the human genome and elucidating their involvement in cancer, understanding the relationship between sequence-based regulatory features and expression patterns from alternative promoters, and developing high throughput assays to identify silencer elements in the human genome. All research avenues converge on the identification of transcription factor binding sites, which are the basic components of gene regulation. Approaches to identify proteins that bind to these regulatory sites are underway for all three of the above research areas. During the course of our work, novel motifs were implicated as silencers and new biological insights were revealed for the genomic structure of alternative promoters. A collaborative effort has been established to define regulatory networks that control gene expression in pathways involved in cancer. These studies will address the methodology of network modeling and identify new targets for cancer diagnostics and testing. These targets are being identified through computational approaches. Experimental follow-up is being done using bisulfite sequencing to assess aberrant methylation of promoter regions, in collaboration with the NIH Sequencing Facility. The analysis aims to study the methylation patterns of promoters in ovarian cancer compared to normal tissue.

基因组功能分析组的主要目的是鉴定脊椎动物基因组中的顺式和反式作用功能元件。寻找这些元素的方法包括计算和实验成分，包括全基因组比较分析、基于机器学习技术的预测和实验测试。主要研究领域包括鉴定人类基因组中的双向启动子并阐明其与癌症的关系，理解基于序列的调控特征与替代启动子的表达模式之间的关系，以及开发高通量测定方法来鉴定人类基因组中的沉默元件。所有的研究途径都集中在转录因子结合位点的鉴定上，而转录因子结合位点是基因调控的基本组成部分。在上述三个研究领域，鉴定与这些调控位点结合的蛋白质的方法正在进行中。在我们的工作过程中，新的基序被认为是沉默者，并为替代启动子的基因组结构揭示了新的生物学见解。已经建立了一项合作努力，以确定控制癌症途径中基因表达的调节网络。这些研究将解决网络建模的方法，并确定癌症诊断和测试的新目标。这些目标是通过计算方法确定的。与NIH测序设施合作，正在使用亚硫酸酯测序来评估启动子区域的异常甲基化。该分析旨在研究与正常组织相比，卵巢癌启动子的甲基化模式。