Chromatin-modifying enzymes as modulators of reprogramming (original) (raw)

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Primary accessions

Gene Expression Omnibus

Data deposits

The microarray and ChIP-seq data have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus (GEO) and are accessible through GEO Series accession numbers GSE29253 and GSE35791.

Change history

Author name for B.O.M. was corrected.

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Acknowledgements

We thank G. Hu and S. J. Elledge for providing the MSCV-PM vector, K. Ng and M. W. Lensch for teratoma injections and assessment and S. Loewer for discussions. We also thank E. Olhava and Epizyme Inc. for synthesizing and providing the DOT1L inhibitor, EPZ004777. G.Q.D. is an investigator of the Howard Hughes Medical Institute. Research was funded by grants from the US National Institutes of Health (NIH) to S.A.A. (CA140575) and G.Q.D., and the CHB Stem Cell Program.

Author information

Authors and Affiliations

  1. Division of Pediatric Hematology and Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Children’s Hospital Boston and Dana Farber Cancer Institute, Boston, 02115, Massachusetts, USA
    Tamer T. Onder, Anne Cherry, Patrick Cahan, Juli Unternaehrer & George Q. Daley
  2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Tamer T. Onder, Anne Cherry, Patrick Cahan, Juli Unternaehrer & George Q. Daley
  3. Harvard Stem Cell Institute, Cambridge, 02138, Massachusetts, USA
    Tamer T. Onder, Anne Cherry, Nan Zhu, Kathrin M. Bernt, Patrick Cahan, Juli Unternaehrer, Scott A. Armstrong & George Q. Daley
  4. Stem Cell Program, Children’s Hospital Boston, Boston, 02115, Massachusetts, USA
    Tamer T. Onder, Anne Cherry, Patrick Cahan, Juli Unternaehrer & George Q. Daley
  5. German Cancer Research Center, Heidelberg, 69120, Germany,
    Nergis Kara
  6. Division of Hematology/Oncology, Children’s Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Amit U. Sinha, Nan Zhu, Kathrin M. Bernt, Scott A. Armstrong & George Q. Daley
  7. Department of Pediatric Oncology, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Amit U. Sinha, Nan Zhu, Kathrin M. Bernt & Scott A. Armstrong
  8. Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06800, Turkey
    B. Ogan Mancarci
  9. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA
    Piyush B. Gupta & Eric S. Lander
  10. Whitehead Institute for Biomedical Research, Cambridge, 02142, Massachusetts, USA
    Piyush B. Gupta
  11. The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA
    Eric S. Lander
  12. Department of Systems Biology, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Eric S. Lander
  13. Division of Hematology, Brigham and Women's Hospital, Boston, 02115, Massachusetts, USA
    George Q. Daley
  14. Howard Hughes Medical Institute, Chevy Chase, 20815, Maryland, USA
    George Q. Daley

Authors

  1. Tamer T. Onder
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  2. Nergis Kara
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  3. Anne Cherry
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  4. Amit U. Sinha
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  5. Nan Zhu
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  6. Kathrin M. Bernt
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  7. Patrick Cahan
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  8. B. Ogan Mancarci
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  9. Juli Unternaehrer
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  10. Piyush B. Gupta
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  11. Eric S. Lander
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  12. Scott A. Armstrong
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  13. George Q. Daley
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Contributions

T.T.O. performed project planning, experimental work, data interpretation and preparation of the manuscript. N.K., A.C, N.Z., J.U. and B.O.M. performed experimental work. P.C. and A.U.S. participated in data analysis. K.M.B. and S.A.A. provided critical materials and participated in the preparation of the manuscript. P.B.G. and E.S.L., participated in data acquisition, data interpretation and preparation of the manuscript. G.Q.D. supervised research and participated in project planning, data interpretation and preparation of the manuscript.

Corresponding author

Correspondence toGeorge Q. Daley.

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Competing interests

S.A.A. is a consultant for Epizyme Inc. G.Q.D. is a member of the scientific advisory boards and holds stock in or receives consulting fees from the following companies: Johnson & Johnson, Verastem, Epizyme, iPierian, Solasia KK and MPM Capital, LLP.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-22. (PDF 1698 kb)

Supplementary Table 1

This table contains a list of all the shRNA sequences used. (XLS 21 kb)

Supplementary Table 2

This table contains a list of qRT-PCR primers used. (XLS 11 kb)

Supplementary Table 3

This table contains genes upregulated and downregulated upon Dot1L inhibition during reprogramming based on gene expression profiling. (XLS 56 kb)

Supplementary Table 4

This table contains the enrichment scores for H3K79me2 and H3K27me3 Chip-seq and lists of genes significantly enriched in the indicated cell populations. (XLS 6867 kb)

Supplementary Table 5

This table shows gene sets significantly enriched in the gene set overlap analysis. (XLS 635 kb)

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Onder, T., Kara, N., Cherry, A. et al. Chromatin-modifying enzymes as modulators of reprogramming.Nature 483, 598–602 (2012). https://doi.org/10.1038/nature10953

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