Journal
SCIENCE
Volume 342, Issue 6161, Pages 948-953Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1236083
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Funding
- National Cancer Institute (Physical Sciences-Oncology Center at MIT) [U54CA143874]
- National Human Genome Research Institute [HG003143]
- Human Frontier Science Program
- W. M. Keck Foundation
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Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.
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