Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins (original) (raw)

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Acknowledgements

This work was supported by a National Institutes of Health (NIH) Director's Pioneer Award DP1 GM105378 (to J.K.J.), NIH P50 HG005550 (to J.K.J.), NIH R01 HD053808 (to M.F.W.), NIH R01 HD045595 (to M.F.W.), NIH R01 CA169316 (to J.F.C.), NIH F32 GM105189 (to S.Q.T.), Defense Advanced Research Projects Agency (DARPA) W911NF-11-2-0056 (to J.K.J.), the Karen Osney Brownstein Endowed Chair (to J.F.C.), the Jim and Ann Orr Massachusetts General Hospital (MGH) Research Scholar Award (to J.K.J.) and a US National Science Foundation Graduate Research Fellowship (to M.L.M.). We thank the MGH Nucleic Acid Quantitation Core (supported by NIH P30 NS45776) for use of their real-time PCR machine.

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Author notes

  1. Morgan L Maeder and James F Angstman: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Morgan L Maeder, James F Angstman, Samantha J Linder, Vincent M Cascio, Shengdar Q Tsai, Quan H Ho, Jeffry D Sander, Deepak Reyon, Bradley E Bernstein & J Keith Joung
  2. Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Morgan L Maeder, James F Angstman, Samantha J Linder, Vincent M Cascio, Shengdar Q Tsai, Jeffry D Sander, Deepak Reyon & J Keith Joung
  3. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA
    Morgan L Maeder & J Keith Joung
  4. Department of Molecular and Cellular Biology, Graduate Program in Molecules, Cells and Organisms, Harvard University, Cambridge, Massachusetts, USA
    James F Angstman
  5. Department of Reproductive Medicine, School of Medicine, University of California, San Diego, La Jolla, California, USA
    Marcy E Richardson & Miles F Wilkinson
  6. Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
    Shengdar Q Tsai, Jeffry D Sander, Deepak Reyon, Bradley E Bernstein & J Keith Joung
  7. Howard Hughes Medical Institute, Chevy Chase, Maryland, USA
    Bradley E Bernstein
  8. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
    Bradley E Bernstein
  9. Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA
    Joseph F Costello
  10. Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA
    Miles F Wilkinson

Authors

  1. Morgan L Maeder
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  2. James F Angstman
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  3. Marcy E Richardson
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  4. Samantha J Linder
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  5. Vincent M Cascio
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  6. Shengdar Q Tsai
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  7. Quan H Ho
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  8. Jeffry D Sander
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  9. Deepak Reyon
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  10. Bradley E Bernstein
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  11. Joseph F Costello
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  12. Miles F Wilkinson
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  13. J Keith Joung
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Contributions

M.L.M., J.F.A., M.E.R., B.E.B., J.F.C., M.F.W. and J.K.J. designed experiments. M.L.M., J.F.A., M.E.R., S.J.L., V.M.C., S.Q.T., Q.H.H., J.D.S. and D.R. conducted experiments. M.L.M., J.F.A., M.E.R., B.E.B., J.F.C., M.F.W. and J.K.J. wrote the paper.

Corresponding author

Correspondence toJ Keith Joung.

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Competing interests

M.L.M., J.F.A. and J.K.J. have filed a provisional patent application covering the TALE-TET fusion proteins. J.K.J. has a financial interest in Transposagen Biopharmaceuticals. J.K.J.'s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies.

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Maeder, M., Angstman, J., Richardson, M. et al. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins.Nat Biotechnol 31, 1137–1142 (2013). https://doi.org/10.1038/nbt.2726

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