XDevelopmental fate and cellular maturity encoded in human regulatory DNA landscapes

Andrew B. Stergachis, Shane Neph, Alex Reynolds, Richard Humbert, Brady Miller, Sharon L. Paige, Benjamin Vernot, Jeffrey B. Cheng, Robert E. Thurman, Richard Sandstrom, Eric Haugen, Shelly Heimfeld, Charles E. Murry, Joshua M. Akey, John A. Stamatoyannopoulos

Research output: Contribution to journalArticlepeer-review

255 Scopus citations


Cellular-state information between generations of developing cells may be propagated via regulatory regions. We report consistent patterns of gain and loss of DNase I-hypersensitive sites (DHSs) as cells progress from embryonic stem cells (ESCs) to terminal fates. DHS patterns alone convey rich information about cell fate and lineage relationships distinct from information conveyed by gene expression. Developing cells share a proportion of their DHS landscapes with ESCs; that proportion decreases continuously in each cell type as differentiation progresses, providing a quantitative benchmark of developmental maturity. Developmentally stable DHSs densely encode binding sites for transcription factors involved in autoregulatory feedback circuits. In contrast to normal cells, cancer cells extensively reactivate silenced ESC DHSs and those from developmental programs external to the cell lineage from which the malignancy derives. Our results point to changes in regulatory DNA landscapes as quantitative indicators of cell-fate transitions, lineage relationships, and dysfunction. PaperClip

Original languageEnglish (US)
Pages (from-to)X888-903
Issue number4
StatePublished - Aug 15 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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