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

doi:10.1016/j.cell.2013.07.020

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 journal › Article › peer-review

266 Scopus citations

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. PaperClip

Original language	English (US)
Pages (from-to)	X888-903
Journal	Cell
Volume	154
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2013.07.020
State	Published - Aug 15 2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2013.07.020

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Stergachis, A. B., Neph, S., Reynolds, A., Humbert, R., Miller, B., Paige, S. L., Vernot, B., Cheng, J. B., Thurman, R. E., Sandstrom, R., Haugen, E., Heimfeld, S., Murry, C. E., Akey, J. M., & Stamatoyannopoulos, J. A. (2013). XDevelopmental fate and cellular maturity encoded in human regulatory DNA landscapes. Cell, 154(4), X888-903. https://doi.org/10.1016/j.cell.2013.07.020

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title = "XDevelopmental fate and cellular maturity encoded in human regulatory DNA landscapes",

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. PaperClip",

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

note = "Funding Information: This work was supported by NIH grants U54HG004592, U54HG007010, and U01ES017156 to J.A.S.; NIH grant P30DK056465 to S.H.; and NIH grants P01GM081719, U01HL100405, P01HL094374, and R01HL084642 to C.E.M. We thank many colleagues, particularly Joseph Costello (UCSF), for contributing cells for DNase I mapping and expression profiling. A.B.S. was supported by grant FDK095678A from NIDDK. S.L.P. was supported by NHLBI grant F30HL095343. We thank Rae Senarighi (UW) for expert assistance with graphic design. All data from this study are available through the ENCODE data repository at UCSC ( http://www.encodeproject.org ) and the Roadmap Epigenomics data repository at NCBI ( http://www.ncbi.nlm.nih.gov/epigenomics ). All data from this study are free to use and are not subject to consortium embargo dates. ",

year = "2013",

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doi = "10.1016/j.cell.2013.07.020",

language = "English (US)",

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T1 - XDevelopmental fate and cellular maturity encoded in human regulatory DNA landscapes

AU - Stergachis, Andrew B.

AU - Neph, Shane

AU - Reynolds, Alex

AU - Humbert, Richard

AU - Miller, Brady

AU - Paige, Sharon L.

AU - Vernot, Benjamin

AU - Cheng, Jeffrey B.

AU - Thurman, Robert E.

AU - Sandstrom, Richard

AU - Haugen, Eric

AU - Heimfeld, Shelly

AU - Murry, Charles E.

AU - Akey, Joshua M.

AU - Stamatoyannopoulos, John A.

N1 - Funding Information: This work was supported by NIH grants U54HG004592, U54HG007010, and U01ES017156 to J.A.S.; NIH grant P30DK056465 to S.H.; and NIH grants P01GM081719, U01HL100405, P01HL094374, and R01HL084642 to C.E.M. We thank many colleagues, particularly Joseph Costello (UCSF), for contributing cells for DNase I mapping and expression profiling. A.B.S. was supported by grant FDK095678A from NIDDK. S.L.P. was supported by NHLBI grant F30HL095343. We thank Rae Senarighi (UW) for expert assistance with graphic design. All data from this study are available through the ENCODE data repository at UCSC ( http://www.encodeproject.org ) and the Roadmap Epigenomics data repository at NCBI ( http://www.ncbi.nlm.nih.gov/epigenomics ). All data from this study are free to use and are not subject to consortium embargo dates.

PY - 2013/8/15

Y1 - 2013/8/15

N2 - 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

AB - 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

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VL - 154

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JO - Cell

JF - Cell

IS - 4

ER -

XDevelopmental fate and cellular maturity encoded in human regulatory DNA landscapes

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