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

Jiang Zhu, Mazhar Adli*, James Y. Zou, Griet Verstappen, Michael Coyne, Xiaolan Zhang, Timothy Durham, Mohammad Miri, Vikram Deshpande, Philip L. De Jager, David A. Bennett, Joseph A. Houmard, Deborah M. Muoio, Tamer T. Onder, Ray Camahort, Chad A. Cowan, Alexander Meissner, Charles B. Epstein, Noam Shoresh, Bradley E. Bernstein

*Corresponding author for this work

Research output: Contribution to journalArticle

340 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)642-654
Number of pages13
JournalCell
Volume152
Issue number3
DOIs
StatePublished - Jan 31 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Zhu, J., Adli, M., Zou, J. Y., Verstappen, G., Coyne, M., Zhang, X., Durham, T., Miri, M., Deshpande, V., De Jager, P. L., Bennett, D. A., Houmard, J. A., Muoio, D. M., Onder, T. T., Camahort, R., Cowan, C. A., Meissner, A., Epstein, C. B., Shoresh, N., & Bernstein, B. E. (2013). Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell, 152(3), 642-654. https://doi.org/10.1016/j.cell.2012.12.033