Genomic-Functional Analyses-Conserved Noncoding Regions

基因组功能分析保守的非编码区域

• 批准号: 7148000
• 负责人: Laura L Elnitski
• 金额: --
• 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/7148000
• 关键词: CpG islands; animal genetic material tag; binding sites; biochemical evolution; bioinformatics; computational biology; functional /structural genomics; gene expression; genetic regulatory element; human genetic material tag; microRNAs; microarray technology; molecular biology information system; nucleic acid sequence; species difference; transcription factor

The major aims of the Genomic Functional Analysis Section are to identify cis-and trans-acting functional elements in vertebrate genomes using comparative analyses. The approach utilizes multi-species, whole-genome sequence alignments to identify conserved noncoding regions, examine patterns of sequence mutation within those elements, and test for changes in expression levels that correspond to changes in the sequences acquired through speciation events. Functional elements under consideration include any elements that comprise collections of transcription factor binding sites such as enhancers, silencers, promoters, and microRNA regulatory regions, elements that are exceptionally conserved, such as ultra-conserved elements, or those that contain uncharacterized structural features such as origins of replication. Collaborative efforts of mine with Penn State University have resulted in evolutionary analyses of promoters that study selection on TATA motifs or CpG islands by using multispecies sequence alignments of human/dog/mouse/chicken. A second study also utilizes sequence comparison to find putative regulatory motifs that control the expression of microRNA from nongenic locations. A related collaborative effort, with NHGRI, involves building a database to house microarray data from the ENCODE consortium. These important data contain information on transcription factor binding sites identified through ChIP-chip assays. The data are used as positive controls for the aforementioned predictions of genomic regulatory regions and for the identification of regions that are targets for future experimental analyses.

基因组功能分析部分的主要目的是通过比较分析来鉴定脊椎动物基因组中的顺式和反式作用的功能元件。该方法利用多物种，全基因组序列比对，以确定保守的非编码区，检查这些元素内的序列突变模式，并测试表达水平的变化，对应于通过物种形成事件获得的序列的变化。所考虑的功能元件包括包含转录因子结合位点的集合的任何元件，例如增强子、沉默子、启动子和微小RNA调控区，异常保守的元件，例如超保守元件，或包含未表征的结构特征例如复制起点的那些元件。 我与宾夕法尼亚州立大学的合作成果是对启动子进行了进化分析，通过使用人/狗/小鼠/鸡的多物种序列比对，研究了TATA基序或CpG岛上的选择。第二项研究还利用序列比较来找到控制非基因位置microRNA表达的假定调控基序。与NHGRI的一项相关的合作工作涉及建立一个数据库来存储来自ENCODE联盟的微阵列数据。这些重要的数据包含通过ChIP芯片分析确定的转录因子结合位点的信息。这些数据被用作上述基因组调控区域预测的阳性对照，并用于鉴定作为未来实验分析目标的区域。