权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Expression and Impact of Interspersed Repeats

散布重复序列的表达和影响

基本信息

批准号：
9816738
负责人：
KATHLEEN H BURNS
金额：
$ 32.75万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-24 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9816738
关键词：
Affect Alleles Amber Area Binding Cells Cellular biology Complex Conflict (Psychology)DNA DNA Insertion Elements DNA Methylation DNA Transposable Elements Data Development Disease Disease model Double-Stranded RNA Elements Embryo Endogenous Retroviruses Epigenetic Process Experimental Models Fertility Gene Expression Gene Expression Regulation Gene Silencing Genes Genetic Genetic Diseases Genetic Transcription Genome Heterochromatin Human Immune response Individual Infectious Agent Interferon Type II Long Interspersed Elements Measures Messenger RNA Modernization Molecular Mutagens Mutation Nuclear Export Outcome Pathway interactions Phenotype Proliferating Proteins Quantitative Trait Loci RNA RNA Editing Regulation Retroelements Retrotransposition Retrotransposon Reverse Transcription Role SETDB1 gene Short Interspersed Nucleotide Elements Side Signal Transduction Site Surveys Testing Tissues Trans-Activators Transcript Transcriptional Regulation Variant Zinc Fingers differential expression genetic variant genome editing genome wide association study human disease human tissue mRNA Export pathogen recruit response sensor transcriptome sequencing

项目摘要

Summary Endogenous retroviruses and related transposable elements make up much of our genome, and active forms persist as long interspersed element-1 (LINE-1, L1) retrotransposons and the elements it mobilizes. These are self-propagating sequences which copy themselves through the reverse transcription of RNA intermediates. We have developed elaborate mechanisms to silence their transcription and limit their proliferation. However, a careful approach to RNAseq analysis reveals that that a subset of individual transposon loci (ITL) escape silencing and are transcriptionally active. In a survey of normal human cells, we identify both constitutive and variably expressed ITL. Our ability to measure these transcripts provides a unique opportunity to examine this host-pathogen relationship and its role in gene regulation. Here, we propose to test the hypothesis that retroelement expression (or lack thereof) is an indicator of specific regulatory mechanisms with cis-acting effects on neighboring genes. We propose to define the landscape of expressed retrotransposons in humans; demonstrate molecular mechanisms of transcriptional silencing and escape; and probe how these mechanisms affect gene expression in human ‘epigenetic’ diseases. We will use genome editing strategies to test whether altering ITL sequences affects neighboring gene expression. Finally, we will develop approaches to study prevalent, highly-expressed short interspersed elements (SINEs) to assess their potential for retrotransposition, determine whether they are targets of RNA editing or dsRNA sensing pathways, and test their interactions with cellular mRNAs in trans. These studies will be among the first to delve into the expression and function of a broad range of retrotransposon intermediates in human cells.

总结