Format

Send to

Choose Destination
Cell. 2013 Aug 15;154(4):888-903. doi: 10.1016/j.cell.2013.07.020.

Developmental fate and cellular maturity encoded in human regulatory DNA landscapes.

Author information

1
Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
2
Department of Medicine, Division of Hematology University of Washington, Seattle, WA 98195, USA.
3
Department of Pathology, University of Washington, Seattle, WA 98109, USA.
4
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
5
Department of Dermatology, University of California, San Francisco, CA 94143, USA.
6
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
7
Department of Bioengineering, University of Washington, Seattle, WA 98109, USA.
8
Department of Medicine, Division of Cardiology University of Washington, Seattle, WA 98195, USA.
9
Department of Medicine, Division of Oncology University of Washington, Seattle, WA 98195, USA.
#
Contributed equally

Abstract

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.

PMID:
23953118
PMCID:
PMC3962256
DOI:
10.1016/j.cell.2013.07.020
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center