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Chemical and Light-Inducible Multiplex Epigenome Editing

化学和光诱导多重表观基因组编辑

基本信息

批准号：
9805973
负责人：
Fu-Sen Liang
金额：
$ 23.3万
依托单位：
CASE WESTERN RESERVE 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：
2019-07-15 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9805973
关键词：
Acetylation Address Biological Biological Process Breast Cancer Cell Cells Chemicals Chimeric Proteins Chromatin Structure Clustered Regularly Interspaced Short Palindromic Repeats DNA DNA Methylation Development EP300 gene Effectiveness Epigenetic Process Event Gene Activation Gene Expression Gene Expression Regulation Generations Genes Genome Goals Guide RNA Heterodimerization Histone Acetylation Individual Kinetics Lead Light Malignant Neoplasms Methods Modification Mutation Pathway interactions Play Processed Genes Proteins Regulatory Pathway Research Role Specificity Staphylococcus aureus Streptococcus pyogenes System Technology Testing Therapeutic Therapeutic Effect Tumor Suppressor Genes Work anti-cancer base cancer cell chromatin remodeling demethylation developmental disease epigenetic regulation epigenome epigenome editing histone modification human disease innovation insight interest new technology next generation novel therapeutic intervention recruit small molecule spatiotemporal success tool

项目摘要

Project Summary The objective of this proposal is to develop new tools to independently and spatiotemporally manipulate distinct epigenetic regulatory mechanisms at defined gene loci. Epigenetic modifications and chromatin structures regulate gene activity. Alteration of epigenetic pathways and mutations in epigenetic regulators contribute to many developmental diseases and cancers. DNA methylation and histone modification have been shown to play important roles in gene activation. Several studies suggest that these epigenetic pathways are orchestrated to regulate activity-gene expression. However, current methods are limited to precisely dissect the functional relationship between these distinct epigenetic regulatory mechanisms. To address this limitation, we propose to develop unique chemical and light inducible methods that integrate dCas9/gRNA-guided targeting with the chemically induced proximity (CIP) technology to individually or simultaneously control different layers of epigenetic regulations (e.g., H3K27 acetylation and DNA demethylation). We will use this new technology to study their functional interplays and test multiplex epigenetic editing in the epigenome. After finishing this work, we expect to establish unique tools that will significantly contribute to the studies of epigenetic regulation in gene activation and offer new directions in developing new epigenetic-based therapies.

项目总结