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    Optogenetic inhibitor of the transcription factor CREB

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    Available after 11/19/2017 (847.1Kb)
    Issue Date
    2016-11-19
    Author
    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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    Abstract
    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.
    URI
    http://hdl.handle.net/1808/23209
    DOI
    https://doi.org/10.1016/j.chembiol.2015.09.018
    Collections
    • Molecular Biosciences Scholarly Works [581]
    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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    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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