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Cell. 2013 Jan 31;152(3):642-54. doi: 10.1016/j.cell.2012.12.033. Epub 2013 Jan 17.

Genome-wide chromatin state transitions associated with developmental and environmental cues.

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  • 1Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Abstract

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
23333102
[PubMed - indexed for MEDLINE]
PMCID:
PMC3563935
Free PMC Article

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