Recently, genomes have been recognized to adopt preferred physical architectures that are evolutionarily conserved and cell type specific. We developed a method for characterizing long-range inter- and intra- chromosomal interactions on a genome-wide scale. Our method is based on chromatin conformation capture (3C) but unlike 3C (or other derivative technologies), makes no a priori assumptions regarding interacting genetic elements. Due to the large size of mammalian genomes we initially validated our approach in haploid Saccharomyces cerevisiae. In this application we propose to use this method to understand the relationship between genome architecture and allele specific expression in mammalian development.

Public Health Relevance

Very little is known about how cells interpret phenotype from genotype. One important waypoint in this interpretation is the establishment of cell-type specific genome topologies. We have developed a new method for characterizing the architecture of whole genomes. With further development we believe that our method will provide a physical annotation to cell state, and will fundamentally advance our understanding of cell biology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM098039-03
Application #
8460150
Study Section
Special Emphasis Panel (ZRG1-GGG-M (50))
Program Officer
Hoodbhoy, Tanya
Project Start
2011-05-30
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
3
Fiscal Year
2013
Total Cost
$586,998
Indirect Cost
$232,481
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Ma, Wenxiu; Noble, William S; Bailey, Timothy L (2014) Motif-based analysis of large nucleotide data sets using MEME-ChIP. Nat Protoc 9:1428-50
Deng, Xinxian; Berletch, Joel B; Nguyen, Di K et al. (2014) X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet 15:367-78
Witten, Daniela M; Noble, William Stafford (2012) On the assessment of statistical significance of three-dimensional colocalization of sets of genomic elements. Nucleic Acids Res 40:3849-55