Journal
CELL
Volume 152, Issue 3, Pages 642-654Publisher
CELL PRESS
DOI: 10.1016/j.cell.2012.12.033
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Funding
- NIH Common Fund [U01 ES017155]
- National Human Genome Research Institute [U54 HG004570]
- National Heart, Lung and Blood Institute [U01 HL100395]
- National Institute on Aging [P30 AG10161]
- Howard Hughes Medical Institute
- Starr Cancer Consortium
- Burroughs Wellcome Fund
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Differences in chromatin organization are key to the multiplicity of cell states that arise from a single genetic background, yet the landscapes of in vivo tissues remain largely uncharted. Here, we mapped chromatin genome-wide in a large and diverse collection of human tissues and stem cells. The maps yield unprecedented annotations of functional genomic elements and their regulation across developmental stages, lineages, and cellular environments. They also reveal global features of the epigenome, related to nuclear architecture, that also vary across cellular phenotypes. Specifically, developmental specification is accompanied by progressive chromatin restriction as the default state transitions from dynamic remodeling to generalized compaction. Exposure to serum in vitro triggers a distinct transition that involves de novo establishment of domains with features of constitutive heterochromatin. We describe how these global chromatin state transitions relate to chromosome and nuclear architecture, and discuss their implications for lineage fidelity, cellular senescence, and reprogramming.
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