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Development of methods for multi-omic analysis of DNA methylation and chromatin architecture in single cells

单细胞 DNA 甲基化和染色质结构多组学分析方法的开发

基本信息

批准号：
10200114
负责人：
Jesse R Dixon
金额：
$ 106.4万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
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：
2019-09-06 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10200114
关键词：
3-Dimensional Algorithms Architecture Binding Binding Sites Biological CCCTC-binding factor Cell Cycle Cell Line Cells Chemicals Chromatin Chromatin Loop Chromatin Structure Classification Complex Cultured Cells Cytosine DNA DNA Methylation DNA analysis Data Data Set Development Dimensions Disease Enhancers Epigenetic Process Gene Expression Gene Expression Regulation Generations Genome Genomic DNA Genomics Goals Heterogeneity Hi-C Human Human Development Human Genome Human body In Vitro Individual Knowledge Ligation Malignant Neoplasms Maps Methods Methylation Modification Molecular Conformation Organism Pattern Play Population Proteins Regulatory Element Research Personnel Resolution Role Technology Tissue Sample Tissues cell type chromosome conformation capture cost epigenomics human tissue in silico in vivo method development methylome multiple omics novel strategies promoter reconstruction single cell analysis transcriptome transcriptomics virtual

项目摘要

Project Summary/Abstract Chromatin organization and epigenomic modifications such as cytosine methylation play instrumental roles in gene regulation during human development and in healthy and disease states. Although the genome is nearly identical in each cell in the human body, chromatin conformation and cytosine DNA methylation are highly dynamic across cell types and during development. Previous studies showed that chromatin looping can be regulated by cytosine methylation. However, our current state of knowledge of the interactions between chromatin organization and DNA methylation is built on analyzing cultured cells and bulk tissues. The interaction between cell-type specific chromatin looping and methylation in heterogeneous tissues remain largely unexplored. This project will develop single-cell multi-omic methods to jointly analyze chromatin conformation and cytosine methylation from the same cell. The methods will lead to high quality cell-type specific chromatin conformation maps of human tissue, and the analysis of the relationship between chromatin conformation and cytosine methylation. If successful, the proposed methods will greatly facilitate the study of gene regulation in complex human tissues and in heterogeneous diseases such as cancer.

项目总结/摘要染色质组织和表观基因组修饰，如胞嘧啶甲基化发挥工具作用在人类发育过程中以及在健康和疾病状态下的基因调控。尽管基因组是在人体的每个细胞中，染色质构象和胞嘧啶DNA甲基化几乎是相同的。以前的研究表明，染色质循环在细胞类型和发育过程中是高度动态的。可以通过胞嘧啶甲基化来调节。然而，我们目前对这种相互作用的了解，染色质组织和DNA甲基化之间的联系建立在分析培养细胞和大块组织的基础上。异质组织中细胞类型特异性染色质成环与甲基化的相互作用该项目将开发单细胞多组学方法，染色质构象和胞嘧啶甲基化。这些方法将导致高质量的人组织细胞类型特异性染色质构象图及其相关性分析染色质构象和胞嘧啶甲基化之间的关系。如果成功，所提出的方法将大大促进复杂人体组织和异质性疾病中基因调控的研究，癌