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 #
5R01GM098039-02
Application #
8269673
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
2012-05-01
Budget End
2013-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$606,054
Indirect Cost
$238,678
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Berletch, Joel B; Ma, Wenxiu; Yang, Fan et al. (2015) Identification of genes escaping X inactivation by allelic expression analysis in a novel hybrid mouse model. Data Brief 5:761-9
Yang, Fan; Deng, Xinxian; Ma, Wenxiu et al. (2015) The lncRNA Firre anchors the inactive X chromosome to the nucleolus by binding CTCF and maintains H3K27me3 methylation. Genome Biol 16:52
Deng, Xinxian; Ma, Wenxiu; Ramani, Vijay et al. (2015) Bipartite structure of the inactive mouse X chromosome. Genome Biol 16:152
Berletch, Joel B; Ma, Wenxiu; Yang, Fan et al. (2015) Escape from X inactivation varies in mouse tissues. PLoS Genet 11:e1005079
Ma, Wenxiu; Ay, Ferhat; Lee, Choli et al. (2015) Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes. Nat Methods 12:71-8
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
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; Ma, Wenxiu et al. (2013) Mammalian X upregulation is associated with enhanced transcription initiation, RNA half-life, and MOF-mediated H4K16 acetylation. Dev Cell 25:55-68
Duan, Zhijun; Blau, Carl Anthony (2012) The genome in space and time: does form always follow function? How does the spatial and temporal organization of a eukaryotic genome reflect and influence its functions? Bioessays 34:800-10
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

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