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BI Human Reference Epigenome Mapping Project: Characterization of DNA methylation by RRBS

ABSTRACT: Characterization of the reference epigenome in humans in a diverse panel of ES cells, tissue stem cells, reprogrammed stem cells, primary cells and tissues. **************** For data usage terms and conditions, please refer to: http://www.drugabuse.gov/funding/funding-opportunities/nih-common-fund/epigenomics-data-access-policies ****************

ORGANISM(S): Homo sapiens

PROVIDER: GSE25246 | GEO | 2010/11/11

REPOSITORIES: GEO

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Project description:The human embryonic stem cells (hESCs) are a unique model system for investigating the mechanisms of human development due to their ability to replicate indefinitely while retaining the capacity to differentiate into a host of functionally distinct cell types. In addition, these cells could be potentially used as therapeutic agents in regenerative medicine. Differentiation of hESCs involves selective activation or silencing of genes, a process controlled in part by the epigenetic state of the cell. In order to gain a better understanding of the epigenetic mechanisms regulating differentiation of hESCs, and produce general reference epigenome maps of the human cells, we propose to establish an Epigenome Center in San Diego. Our center will be focused on both undifferentiated hESC and four hESC-derived early embryonic cell lineages including extraembryonic endoderm, trophoblast, mesendoderm (a common precursor to mesodermal and endodermal lineages), and mesenchymal cells (a specific mesoderm derivative). We have developed and validated high throughput technologies for mapping the state of DNA methylation and chromatin modifications throughout the genome, and will use these methods to generate high-resolution maps of the reference epigenomes. Specifically, we will grow and differentiate hESCs into multiple lineages, and map DNA methylation sites using a newly developed technology that combines bisulfite conversion and whole genome shotgun sequencing. We will also determine the histone modification status in the genome by performing both ChlP-chip and ChlP-Seq analysis. We will develop advanced statistical and algorithmic solutions to facilitate high-throughput sequencing data analysis, and establish an informatics pipeline for collecting, storage, and distribution of epigenome maps. Finally, we will perform integrated data analysis to identify new epigenetic patterns in the genome that could provide insights in mechanisms of epigenetic regulation. **************** For data usage terms and conditions, please refer to: http://www.drugabuse.gov/funding/funding-opportunities/nih-common-fund/epigenomics-data-access-policies ****************

Project description:The epigenome is the dynamic interface between our changing environment and the static genome, and understanding it is a goal of immense importance to human health. We will map reference cell epigenomes of the brain, breast, blood and approved embryonic stem cells, inclusive of males and females and different racial groups. This cooperative work will transform our understanding of the short and long-lasting consequences of environment impact on human health and disease. We are working cooperatively with other Mapping Centers and the Data Coordination Center (EDACC) to comprehensively map epigenomes of select human cells with significant relevance to complex human disease. Our group, consisting of scientists at UCSF, UC Davis, UCSC and the British Columbia Genome Sciences Centre will focus on cells relevant to human health and complex disease including cells from the blood, brain, breast and U.S. Government-approved lines of human embryonic stem cells. We will incorporate high quality, homogeneous cells from males and females, and two predominant racial groups, and biological replicates of each cell type. Production of comprehensive maps will include 6 histone modifications selected for their opposing roles in regulating active and inactive chromatin, DNA methylation and miRNA and gene expression. This epigenetic data, along with genetic and expression data will be integrated using advanced informatics to address fundamental roles of epigenetics in differentiation, maintenance of cell-type identity and gene expression. Our cell and data production pipeline will incorporate verification and data validation with independent methods, and will operate under a model motivated by increased data production and decrease cost. We summarize the analysis capacity of our instruments and our explicit strategy for data sharing of our proposed REMC-generated resources including biological specimens, protocols, data, software tools and intellectual resources. We envision that our group in conjunction with the other REMC teams, the EDACC, ENCODE, future EHHD (Epigenetics of Human Health and Disease) centers and the NIH Roadmap program will develop methods, tools and reference epigenome maps for the research community that will make the promise of epigenetics in understand and treating human complex disease a reality. Our reference epigenomes will enable new disciplines including human population epigenetics, comparative epigenomics, neuroepigenetics, and therapeutic epigenetics for tissue regeneration and reversal of disease. Contributor: BCCA Genome Sciences Centre **************** For data usage terms and conditions, please refer to: http://www.drugabuse.gov/funding/funding-opportunities/nih-common-fund/epigenomics-data-access-policies ****************

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BI Human Reference Epigenome Mapping Project: Characterization of DNA methylation by RRBS

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