We propose to work cooperatively with other Mapping Centers and the Data Coordination Center (EDACC) funded by this Roadmap mechanism 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 has the broad expertise that this project requires. We 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 (aim 1). 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 (aim 2), DNA methylation (aim 3) and miRNA and gene expression (aim 4). This epigenetic data, along with genetic and expression data will be integrated using advanced informatics (aim 5) 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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZRG1-CB-P (50))
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Tyson, Frederick L
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Zhou, Xin; Li, Daofeng; Lowdon, Rebecca F et al. (2014) methylC Track: visual integration of single-base resolution DNA methylation data on the WashU EpiGenome Browser. Bioinformatics 30:2206-7
Yao, Lijing; Tak, Yu Gyoung; Berman, Benjamin P et al. (2014) Functional annotation of colon cancer risk SNPs. Nat Commun 5:5114
Raney, Brian J; Dreszer, Timothy R; Barber, Galt P et al. (2014) Track data hubs enable visualization of user-defined genome-wide annotations on the UCSC Genome Browser. Bioinformatics 30:1003-5
Nagarajan, Raman P; Zhang, Bo; Bell, Robert J A et al. (2014) Recurrent epimutations activate gene body promoters in primary glioblastoma. Genome Res 24:761-74
Hattori, Takamitsu; Taft, Joseph M; Swist, Kalina M et al. (2013) Recombinant antibodies to histone post-translational modifications. Nat Methods 10:992-5
Sanborn, J Zachary; Salama, Sofie R; Grifford, Mia et al. (2013) Double minute chromosomes in glioblastoma multiforme are revealed by precise reconstruction of oncogenic amplicons. Cancer Res 73:6036-45
Hangauer, Matthew J; Vaughn, Ian W; McManus, Michael T (2013) Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet 9:e1003569
Stevens, Michael; Cheng, Jeffrey B; Li, Daofeng et al. (2013) Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods. Genome Res 23:1541-53
Hirst, Martin (2013) Epigenomics: sequencing the methylome. Methods Mol Biol 973:39-54
Roy, Somdutta; Gascard, Philippe; Dumont, Nancy et al. (2013) Rare somatic cells from human breast tissue exhibit extensive lineage plasticity. Proc Natl Acad Sci U S A 110:4598-603

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