Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay (original) (raw)

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Acknowledgements

The authors would like to thank E.M. LeProust and S. Chen of Agilent for oligonucleotide library synthesis, R.P. Deering for assistance with Sendai virus infections and the staff of the Broad Institute and the Bauer Core facilities for assistance with data generation. This project was supported by funds from the Broad Institute, the Harvard Stem Cell Institute (T.S.M.), National Human Genome Research Institute grant R01HG004037 (M.K.), the Simons Center for Quantitative Biology at Cold Spring Harbor Laboratory (J.B.K.), National Science Foundation (NSF) grant PHY-0957573 (C.G.C., T.T.) and NSF grant PHY-1022140 (A. Mur.).

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Author notes

1. Alexandre Melnikov, Anand Murugan and Xiaolan Zhang: These authors contributed equally to this work.

Authors and Affiliations

1. Broad Institute, Cambridge, Massachusetts, USA
   Alexandre Melnikov, Xiaolan Zhang, Li Wang, Peter Rogov, Soheil Feizi, Andreas Gnirke, Manolis Kellis, Eric S Lander & Tarjei S Mikkelsen
2. Department of Physics, Princeton University, Princeton, New Jersey, USA
   Anand Murugan, Tiberiu Tesileanu & Curtis G Callan Jr
3. Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey, USA
   Tiberiu Tesileanu & Curtis G Callan Jr
4. MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts, USA
   Soheil Feizi & Manolis Kellis
5. Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA
   Justin B Kinney
6. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
   Eric S Lander
7. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
   Eric S Lander
8. Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA
   Tarjei S Mikkelsen

Authors

1. Alexandre Melnikov
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2. Anand Murugan
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3. Xiaolan Zhang
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4. Tiberiu Tesileanu
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5. Li Wang
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6. Peter Rogov
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7. Soheil Feizi
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8. Andreas Gnirke
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9. Curtis G Callan Jr
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10. Justin B Kinney
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11. Manolis Kellis
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12. Eric S Lander
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13. Tarjei S Mikkelsen
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Contributions

A. Mel., X.Z., P.R., A.G. and T.S.M. developed MPRA and performed the molecular biology experiments. L.W. cultured the cells, and performed the plasmid transfections and luciferase assays. A.Mur., T.T., S.F., C.G.C., J.B.K., M.K., E.S.L. and T.S.M. analyzed the data. T.S.M. wrote the main text with substantial input from all authors. C.G.C. and J.B.K. wrote the Supplementary Notes with substantial input from A. Mur. and T.S.M.

Corresponding author

Correspondence toTarjei S Mikkelsen.

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A patent application describing ideas presented in this article has been filed by the Broad Institute.

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Melnikov, A., Murugan, A., Zhang, X. et al. Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay.Nat Biotechnol 30, 271–277 (2012). https://doi.org/10.1038/nbt.2137

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• Received: 23 August 2011
• Accepted: 20 January 2012
• Published: 26 February 2012
• Issue Date: March 2012
• DOI: https://doi.org/10.1038/nbt.2137