Uncovering the epigenetic codes for genome integrity, developmental and environmental interaction.

揭示基因组完整性、发育和环境相互作用的表观遗传密码。

• 批准号: 10223356
• 负责人: XUEHUA ZHONG
• 金额: $ 37.61万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223356
• 关键词: Angiosperms; Animal Model; Animals; Arabidopsis; Biological Models; Biological Process; Caenorhabditis elegans; Chemicals; Chromatin; Code; Common Core; Cytosine; DNA Methylation; Defect; Deposition; Development; Developmental Process; Disease; Drosophila melanogaster; Epigenetic Process; Genome; Human; Knowledge; Malignant Neoplasms; Mammals; Medicine; Modification; Molecular; Organism; Pathologic; Pathologic Processes; Pattern; Phase Transition; Physiological; Physiological Processes; Play; Public Health; Regulator Genes; Research; Role; Saccharomyces cerevisiae; Stimulus; Switch Genes; System; Tissues; epigenetic regulation; genome integrity; insight; null mutation; programs; public health relevance; response

PROJECT SUMMARY Epigenetic modification is an important gene regulatory mechanism and plays quintessential roles in the control of genome integrity, development, environmental responses, and diseases. Despite the large amount of studies describing altered modification patterns in abnormal developmental and pathological tissues, whether they are a cause or a consequence is poorly understood. This proposal dissects molecular mechanism of epigenetic regulation and functional consequences of altered epigenetic patterns under physiological conditions. Specifically, we investigate 1) how chromatin senses and memorizes the environmental stimuli; 2) how an epigenetic switch regulates developmental phase transition; and 3) how epigenetic modification safeguards the genome integrity. We use the flowering plant Arabidopsis, proved to be a robust system for mechanistic epigenetic studies, as our model system. Arabidopsis shares with mammals the common core cytosine DNA methylation machinery that is lacking in other model organisms (e.g. Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster). Importantly, Arabidopsis tolerates null mutations in most epigenetic regulators that are often lethal in animals, providing a significant advantage to investigate in-depth mechanisms under developmental and physiological conditions. As we probe basic principles governing epigenetic regulation that are conserved across eukaryotic organisms, knowledge acquired from our pioneering studies in Arabidopsis will help accelerate progress in deciphering the relevant mechanisms in human. In-depth mechanistic knowledge is crucial for understanding how epigenetic modification contributes to developmental defects and disease. Such knowledge will provide the necessary insight to develop new medicines that target the respective epigenetic processes.

项目总结