The overall aim of this proposal is to establish an integrated Center for creating high-quality reference maps of key epigenotypes in pluripotent, differentiating, and primary differentiated human cells and tissues. The Northwest Reference Epigenome Mapping Center aggregates leading experts in human embryonic stem cell (hESC) biology, lineage-specific differentiation of hESCs, and well-established differentiating and differentiated adult primary tissue systems to establish a substantial capacity for the production of purified cells and tissues for large-scale epigenomic studies. The Center integrates this capacity with an existing high-throughput genomics and informatics infrastructure operating at scale, creating unique synergies that enable genome-scale epigenetic analyses of high-value human primary and progenitor cell types. The Center will perform high-resolution, whole-genome profiling of foundational epigenotypes in project cell types including high-resolution quantification of chromatin structural remodeling, and analysis of DNA methylation at both actively remodeled and silenced regulatory DNA templates. The Center will also profile both small RNA species and conventional gene expression from all study cell types. The Center's informatics and analytical arm will manage project data and its release into consortium and public repositories, and will perform integrative analyses to elucidate the connection between major epigenotypes and dynamic cellular programming of gene expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01ES017156-04
Application #
8098925
Study Section
Special Emphasis Panel (ZRG1-CB-P (50))
Program Officer
Tyson, Frederick L
Project Start
2008-09-29
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$1,440,482
Indirect Cost
Name
University of Washington
Department
Genetics
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Maurano, Matthew T; Wang, Hao; John, Sam et al. (2015) Role of DNA Methylation in Modulating Transcription Factor Occupancy. Cell Rep 12:1184-95
Roadmap Epigenomics Consortium; Kundaje, Anshul; Meuleman, Wouter et al. (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317-30
Maurano, Matthew T; Stamatoyannopoulos, John A (2015) Taking Stock of Regulatory Variation. Cell Syst 1:18-21
Yen, Angela; Kellis, Manolis (2015) Systematic chromatin state comparison of epigenomes associated with diverse properties including sex and tissue type. Nat Commun 6:7973
Maurano, Matthew T; Haugen, Eric; Sandstrom, Richard et al. (2015) Large-scale identification of sequence variants influencing human transcription factor occupancy in vivo. Nat Genet 47:1393-401
Liu, Mingdong; Maurano, Matthew T; Wang, Hao et al. (2015) Genomic discovery of potent chromatin insulators for human gene therapy. Nat Biotechnol 33:198-203
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Neph, Shane; Kuehn, M Scott; Reynolds, Alex P et al. (2012) BEDOPS: high-performance genomic feature operations. Bioinformatics 28:1919-20
Maurano, Matthew T; Humbert, Richard; Rynes, Eric et al. (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science 337:1190-5

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