Cis regulatory elements in the inner ear

内耳中的顺式调节元件

基本信息

批准号：
9111307
负责人：
Olivia Mary Bermingham-McDonogh
金额：
$ 22.96万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9111307
关键词：
Adult Age Aging Antibodies Auditory BMP4 Binding Biological Assay Birds Brain region Cell Count Cell Differentiation process Cell Line Cells ChIP-seq Chromatin Cochlear duct Complex DNA DNase I hypersensitive sites sequencing Defect Deoxyribonuclease I Development Digestion EP300 gene Electroporation Enhancers Equilibrium FGF20 gene Fishes Gene Expression Gene Expression Regulation Genes Genetic Genome Genomics Hair Cells Health Hearing Human Hypersensitivity In Situ Hybridization Knowledge Labyrinth Lead Maps Methods Mus Mutant Strains Mice Natural regeneration Neural Retina Noise Nucleic Acid Regulatory Sequences Organ Pattern Pharmaceutical Preparations Phase Population Process Proteins Protocols documentation Regulation Regulatory Element Reporting Research Role Sampling Sensory Sensory Hair Signal Transduction Signaling Molecule Societies Staging Supporting Cell Techniques Testing Time Tissues Validation Vertebrates Work cell type chromatin modification cognitive development deafness ear development equilibration disorder functional restoration gene therapy hearing impairment high throughput screening inner ear diseases interest mutant non-genetic notch protein novel programs promoter public health relevance transcription factor transcriptome sequencing transgene expression

项目摘要

DESCRIPTION (provided by applicant): Hearing loss is a large health issue in the US with approximately 36 million adults reporting some loss. Much of this deafness is caused by loss of the sensory hair cells in the inner ear either from noise or drug damage or just aging. Much research has aimed at replacing these lost cells. Another approach is to restart the developmental program by which these cells develop to begin with. The inner ear is a highly complex tissue, with many different cell types. Understanding the development of this complex organ will ultimately require characterization of gene expression and its regulation in developing and mature inner ear cell types. DNase I hypersensitivity mapping (DNase I-seq) has recently been developed to map enhancers of genes in particular tissues at particular stages of development. In this proposed research we aim to map the enhancers that are used in the inner ear during development. Knowledge of the way genes are regulated in the inner ear may provide us with additional targets for manipulation in our attempts to restore hearing and balance function. This research proposes to completely characterize the enhancers using DNase I hypersensitivity mapping, RNA-seq and using mutant mice that lack sensory domains to determine which are the critical genes. This will be accomplished with the following three specific aims: Aim 1. Mapping the accessible chromatin in the inner ear at three developmental ages. Aim 2. Mapping DNase I hypersensitive regions in a mutant lacking the sensory domain. Aim 3. Characterization of enhancer activity in explant culture.

描述（由申请人提供）：听力损失是美国的一个重大健康问题，大约有 3600 万成年人报告听力损失，大部分是由于噪音、药物损伤或内耳感觉毛细胞损失造成的。许多研究旨在替代这些丢失的细胞，从而重新启动这些细胞的发育过程。内耳是一个高度复杂的组织，需要了解许多不同的细胞类型。复杂的器官最终需要表征最近开发了 DNase I 超敏图谱 (DNase I-seq)，用于绘制特定组织中特定发育阶段的基因增强子图谱。绘制内耳发育过程中使用的增强子的图谱，了解内耳中基因的调节方式可能为我们尝试恢复听力和平衡功能提供额外的目标。使用 DNA 酶 I超敏性图谱、RNA-seq 以及使用缺乏感觉域的突变小鼠来确定哪些是关键基因。这将通过以下三个具体目标来实现：目标 1. 绘制三个发育年龄的内耳中可接近的染色质。 2. 绘制缺乏感觉域的突变体中的 DNase I 超敏感区域目的 3. 外植体培养中增强子活性的表征。