Optogenetic inhibitor of the transcription factor CREB
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Issue Date
2016-11-19Author
Ali, Ahmed M.
Reis, Jakeb M.
Xia, Yan
Rashid, Asim J.
Mercaldo, Valentina
Walters, Brandon J.
Brechun, Katherine
Borisenko, Vitali
Josselyn, Sheena A.
Karanicolas, John
Woolley, G. Andrew
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
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Show full item recordAbstract
Current approaches for optogenetic control of transcription do not mimic the activity of endogenous transcription factors, which act at numerous sites in the genome in a complex interplay with other factors. Optogenetic control of dominant negative versions of endogenous transcription factors provides a mechanism for mimicking the natural regulation of gene expression. Here we describe opto-DN-CREB, a blue light controlled inhibitor of the transcription factor CREB created by fusing the dominant negative inhibitor A-CREB to photoactive yellow protein (PYP). A light driven conformational change in PYP prevents coiled-coil formation between A-CREB and CREB, thereby activating CREB. Optogenetic control of CREB function was characterized in vitro, in HEK293T cells, and in neurons where blue light enabled control of expression of the CREB targets NR4A2 and c-Fos. Dominant negative inhibitors exist for numerous transcription factors; linking these to optogenetic domains offers a general approach for spatiotemporal control of native transcriptional events.
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Citation
Ali, Ahmed M., Jakeb M. Reis, Yan Xia, Asim J. Rashid, Valentina Mercaldo, Brandon J. Walters, Katherine E. Brechun, Vitali Borisenko, Sheena A. Josselyn, John Karanicolas, and G. Andrew Woolley. "Optogenetic Inhibitor of the Transcription Factor CREB." Chemistry & Biology 22.11 (2015): 1531-539.
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