Genome-wide Chromatin State Transitions Associated with Developmental and Environmental Cues

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. [Display omitted] ► A resource of chromatin state maps for phenotypically diverse human tissues ► Annotation of regulatory elements across developmental stages and environments ► Developmental specification is accompanied by progressive chromatin restriction ► Chromatin architecture changes in cultured cells have implications for reprogramming A large collection of chromatin state maps, representing human cells and tissues in vivo, reveals tissue-specific enhancer-like elements as well as repressive chromatin domains that arise during development or in response to nonphysiologic cellular environments and may present a hindrance to cellular reprogramming.