Multi-chromatic control of mammalian gene expression and signaling
Open Access
- 26 April 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 41 (12), e124
- https://doi.org/10.1093/nar/gkt340
Abstract
The emergence and future of mammalian synthetic biology depends on technologies for orchestrating and custom tailoring complementary gene expression and signaling processes in a predictable manner. Here, we demonstrate for the first time multi-chromatic expression control in mammalian cells by differentially inducing up to three genes in a single cell culture in response to light of different wavelengths. To this end, we developed an ultraviolet B (UVB)-inducible expression system by designing a UVB-responsive split transcription factor based on the Arabidopsis thaliana UVB receptor UVR8 and the WD40 domain of COP1. The system allowed high (up to 800-fold) UVB-induced gene expression in human, monkey, hamster and mouse cells. Based on a quantitative model, we determined critical system parameters. By combining this UVB-responsive system with blue and red light-inducible gene control technology, we demonstrate multi-chromatic multi-gene control by differentially expressing three genes in a single cell culture in mammalian cells, and we apply this system for the multi-chromatic control of angiogenic signaling processes. This portfolio of optogenetic tools enables the design and implementation of synthetic biological networks showing unmatched spatiotemporal precision for future research and biomedical applications.Keywords
This publication has 60 references indexed in Scilit:
- Programmable single-cell mammalian biocomputersNature, 2012
- A designer network coordinating bovine artificial insemination by ovulation-triggered release of implanted spermsJournal of Controlled Release, 2011
- Self-sufficient control of urate homeostasis in mice by a synthetic circuitNature Biotechnology, 2010
- A tunable synthetic mammalian oscillatorNature, 2009
- A synthetic mammalian gene circuit reveals antituberculosis compoundsProceedings of the National Academy of Sciences of the United States of America, 2008
- A Tunable Genetic Switch Based on RNAi and Repressor Proteins for Regulating Gene Expression in Mammalian CellsCell, 2007
- A synthetic time-delay circuit in mammalian cells and miceProceedings of the National Academy of Sciences of the United States of America, 2007
- Hysteresis in a synthetic mammalian gene networkProceedings of the National Academy of Sciences of the United States of America, 2005
- An engineered epigenetic transgene switch in mammalian cellsNature Biotechnology, 2004
- Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.Proceedings of the National Academy of Sciences of the United States of America, 1992