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Cell DOI:10.1016/j.cell.2012.12.033

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

Publication TypeJournal Article
Year of Publication2013
AuthorsZhu, J, Adli, M, Zou, JY, Verstappen, G, Coyne, M, Zhang, X, Durham, T, Miri, M, Deshpande, V, De Jager, PL, Bennett, DA, Houmard, JA, Muoio, DM, Onder, TT, Camahort, R, Cowan, CA, Meissner, A, Epstein, CB, Shoresh, N, Bernstein, BE
Date Published2013 Jan 31
KeywordsCell Aging, Cell Nucleus, Chromatin, Chromatin Assembly and Disassembly, Embryonic Stem Cells, Epigenesis, Genetic, Gene Expression Regulation, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Induced Pluripotent Stem Cells, Organ Specificity

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.


Alternate JournalCell
PubMed ID23333102
PubMed Central IDPMC3563935
Grant ListU01 HL100395 / HL / NHLBI NIH HHS / United States
P30 AG10161 / AG / NIA NIH HHS / United States
R01 DK056112 / DK / NIDDK NIH HHS / United States
R01 AG036042 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
U54 HG004570 / HG / NHGRI NIH HHS / United States
U01 ES017155 / ES / NIEHS NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States