LncRNA regulation of environmental response

LncRNA对环境反应的调节

基本信息

批准号：
9084547
负责人：
Howard Y Chang
金额：
$ 52.96万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-20 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9084547
关键词：
Aflatoxins Alkylating Agents Aromatic Polycyclic Hydrocarbons Arsenic Binding Biological Cells Cellular Stress Chlorinated Hydrocarbons Chromatin DNA DNA Damage DNA Methylation DNA Modification Process DNA Repair Environment Environmental Exposure Epigenetic Process Exposure to Family Gene Expression Gene Expression Regulation Gene Targeting Genes Genetic Transcription Genome Genomics Genotoxic Stress Goals Health Human Indium Lead Maps Mediating Messenger RNA Methods Mutagens Nitrosamines Output Play Post-Translational Protein Processing Proliferating Protein p53 RNA RNA Binding Regulation Regulator Genes Research Role Shapes Signal Transduction Site Specificity Stress Structure TP53 gene Technology Therapeutic Tobacco Toxic Environmental Substances Transcription Alteration Untranslated RNA base chromatin modification chromium hexavalent ion environmental agent environmental stressor epigenome gene induction genome-wide histone modification improved insight loss of function novel programs research study response toxicant transcription factor

项目摘要

DESCRIPTION (provided by applicant): Long noncoding RNAs (lncRNAs) have emerged as a pervasive and important class of regulators of gene expression and chromatin states. We discovered that numerous lncRNAs are induced by DNA damage, and actively regulate the cell's response to DNA damage, including those elicited by environmental toxicants. The long term goal of this project is to understand the regulation and functions of lncRNAs in response to environmental exposures. First, we will identify lncRNAs and open chromatin sites induced by diverse genotoxic agents. Second, we will determine how the DNA damage-inducible lncRNAs modulate the activity of p53, a key transcription factor in the damage response. Third, using two new genomic technologies, we will identify the chromatin regulatory functions and gene targets of toxicant- induced lncRNAs. These experiments will provide key insights into how incipient environmental stress is transmitted into long term changes in gene expression, chromatin states, and ultimately distinct cell fates.

描述（由申请人提供）：长非编码 RNA (lncRNA) 已成为一类普遍且重要的基因表达和染色质状态调节因子。我们发现许多 lncRNA 是由 DNA 损伤诱导的，并积极调节细胞对 DNA 损伤的反应，包括环境毒物引起的反应。该项目的长期目标是了解 lncRNA 对环境暴露的调节和功能。首先，我们将鉴定由不同基因毒性剂诱导的 lncRNA 和开放染色质位点。其次，我们将确定 DNA 损伤诱导型 lncRNA 如何调节 p53（损伤反应中的关键转录因子）的活性。第三，利用两项新的基因组技术，我们将确定毒物诱导的lncRNA的染色质调节功能和基因靶点。这些实验将为研究初期环境压力如何转化为基因表达、染色质状态以及最终不同细胞命运的长期变化提供重要见解。