Abstract
We developed a light-switchable transgene system based on a synthetic, genetically encoded light-switchable transactivator. The transactivator binds promoters upon blue-light exposure and rapidly initiates transcription of target transgenes in mammalian cells and in mice. This transgene system provides a robust and convenient way to spatiotemporally control gene expression and can be used to manipulate many biological processes in living systems with minimal perturbation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Braselmann, S., Graninger, P. & Busslinger, M. Proc. Natl. Acad. Sci. USA 90, 1657–1661 (1993).
Gossen, M. et al. Science 268, 1766–1769 (1995).
Cambridge, S.B., Davis, R.L. & Minden, J.S. Science 277, 825–828 (1997).
Minden, J., Namba, R., Mergliano, J. & Cambridge, S. Sci. STKE 2000, l1 (2000).
Cambridge, S.B. et al. Nat. Methods 6, 527–531 (2009).
Kamei, Y. et al. Nat. Methods 6, 79–81 (2009).
Shimizu-Sato, S., Huq, E., Tepperman, J.M. & Quail, P.H. Nat. Biotechnol. 20, 1041–1044 (2002).
Levskaya, A. et al. Nature 438, 441–442 (2005).
Yazawa, M., Sadaghiani, A.M., Hsueh, B. & Dolmetsch, R.E. Nat. Biotechnol. 27, 941–945 (2009).
Kennedy, M.J. et al. Nat. Methods 7, 973–975 (2010).
Ye, H., Daoud-El Baba, M., Peng, R.W. & Fussenegger, M. Science 332, 1565–1568 (2011).
Hong, M. et al. Structure 16, 1019–1026 (2008).
Zoltowski, B.D. et al. Science 316, 1054–1057 (2007).
Zoltowski, B.D. & Crane, B.R. Biochemistry 47, 7012–7019 (2008).
Lamb, J.S., Zoltowski, B.D., Pabit, S.A., Crane, B.R. & Pollack, L. J. Am. Chem. Soc. 130, 12226–12227 (2008).
Zoltowski, B.D., Vaccaro, B. & Crane, B.R. Nat. Chem. Biol. 5, 827–834 (2009).
Shaw, G. & Kamen, R. Cell 46, 659–667 (1986).
Deisseroth, K. Nat. Methods 8, 26–29 (2011).
Fenno, L., Yizhar, O. & Deisseroth, K. Annu. Rev. Neurosci. 34, 389–412 (2011).
Groskreutz, D.J., Sliwkowski, M.X. & Gorman, C.M. J. Biol. Chem. 269, 6241–6245 (1994).
Liu, F., Song, Y. & Liu, D. Gene Ther. 6, 1258–1266 (1999).
Ferrari, D., Wesselborg, S., Bauer, M.K. & Schulze-Osthoff, K. J. Cell Biol. 139, 1635–1643 (1997).
Acknowledgements
We thank Z.H. Yu and J.Z. Chen for their suggestions, and Z.M. Du, Z.C. Ma, J.H. Wang, W.T. Zhu, X.Y. Feng and Y.Z. Zhao for technical assistance. This work was supported by the National Natural Science Foundation of China (grants 31170815, 31071260 and 90713026), the 863 Program (grant no. 2006AA02Z160), the Fok Ying Tung Education Foundation (grant 111022), the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Dawn Program of Shanghai Education Commission (grant 11SG31), Doctoral Fund of Ministry of Education of China (grant 20100074110010), the Fundamental Research Funds for the Central Universities and the 111 Project (grant B07023).
Author information
Authors and Affiliations
Contributions
Y.Y. conceived of the concept; Y.Y., X.W. and X.C. designed the experiments and analysed the data; X.W. preformed the molecular cloning, protein characterization and cell culture experiments; X.C. preformed animal studies; and Y.Y. wrote the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–15, Supplementary Tables 1–2, Supplementary Note (PDF 1238 kb)
Rights and permissions
About this article
Cite this article
Wang, X., Chen, X. & Yang, Y. Spatiotemporal control of gene expression by a light-switchable transgene system. Nat Methods 9, 266–269 (2012). https://doi.org/10.1038/nmeth.1892
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nmeth.1892
This article is cited by
-
Spatiotemporal control of RNA metabolism and CRISPR–Cas functions using engineered photoswitchable RNA-binding proteins
Nature Protocols (2024)
-
Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases
Nature Nanotechnology (2024)
-
Controlling protein stability with SULI, a highly sensitive tag for stabilization upon light induction
Nature Communications (2023)
-
Design of a palette of SNAP-tag mimics of fluorescent proteins and their use as cell reporters
Cell Discovery (2023)
-
Dimerization processes for light-regulated transcription factor Photozipper visualized by high-speed atomic force microscopy
Scientific Reports (2022)