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Synergistic and tunable human gene activation by combinations of synthetic transcription factors
Open accessAbstract
Mammalian genes are regulated by the cooperative and synergistic actions of many transcription factors. In this study we recapitulate this complex regulation in human cells by targeting endogenous gene promoters, including regions of closed chromatin upstream of silenced genes, with combinations of engineered transcription activator–like effectors (TALEs). These combinations of TALE transcription factors induced substantial gene activation and allowed tuning of gene expression levels that will broadly enable synthetic biology, gene therapy and biotechnology.
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Cited by
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CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.044 · Cited by 3,696
“Naturally occurring and engineered DNAbinding proteins, such as the tetracycline repressor, Gal4, zinc-fingers or the TALE proteins, have been fused to transcription activators and repressors to modulate gene expression (Cong et al., 2012; Deuschle et al., 1995; Gossen and Bujard, 1992; Hathaway et al., 2012; Maeder e…”
BackgroundZFN, TALEN, and CRISPR/Cas-based methods for genome engineering
Gaj, T., Gersbach, C. A., & Barbas, C. F. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2013.04.004 · Cited by 3,820
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Sander, J. D., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2842 · Cited by 3,153
Mali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., Yang, L., & Church, G. M. (2013) · Nature Biotechnology · doi:10.1038/nbt.2675 · Cited by 1,752
Metadata
- Authors
- Perez-Pinera, P., Ousterout, D. G., Brunger, J. M., Farin, A. M., Glass, K. A., Guilak, F., Crawford, G. E., Hartemink, A. J., & Gersbach, C. A.
- Venue
- Nature Methods
- Published
- 2013-02-03
- Volume
- 10
- Issue
- 3
- Pages
- 239-242
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W1965423091
- Cited by
- 242
- References
- 0
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- green
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- Perez-Pinera, P., Ousterout, D. G., Brunger, J. M., Farin, A. M., Glass, K. A., Guilak, F., Crawford, G. E., Hartemink, A. J., & Gersbach, C. A. (2013). Synergistic and tunable human gene activation by combinations of synthetic transcription factors. Nature Methods. https://doi.org/10.1038/nmeth.2361
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