companion website for paper by Zhu et al.

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Although the amount of genome sequence engaged in gene regulatory activity is relatively consistent, the chromatin configurations of the inactive regions varies considerably between cell types. In ES cells (left), inactive regions are diffusely enriched for markers of chromatin exchange and accessibility. In differentiated cells acquired in vivo (middle), inactive loci instead tend to adopt a Polycomb-repressed chromatin state. In differentiated cells cultured in vitro (right), large domains enriched for the heterochromatin marker H3K9me3 arise in regions associated with the nuclear lamina.

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.