A Photodeactivatable Antagonist for Controlling CREB-Dependent Gene Expression

Takuma Imoto; Masafumi Minoshima; Tatsushi Yokoyama; Ben P. Emery; Steven D. Bull; Haruhiko Bito; Kazuya Kikuchi

doi:10.1021/acscentsci.0c00736

A Photodeactivatable Antagonist for Controlling CREB-Dependent Gene Expression

Takuma Imoto, Masafumi Minoshima, Tatsushi Yokoyama, Ben P. Emery, Steven D. Bull, Haruhiko Bito, Kazuya Kikuchi

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

6 Citations (SciVal)

Abstract

A novel photodeactivation strategy for controlling gene expression has been developed based on light-induced activation of cAMP response element binding protein (CREB). Light-induced cleavage of the photoresponsive protecting group of an antagonist of CREB binding protein (CBP) results in photocleaved products with weak binding affinity for CBP. This photodissociation reaction enables protein-protein interactions between CBP and CREB that trigger the formation of a multiprotein transcription complex to turn gene expression "on". This enables irradiation of antagonist-treated HEK293T cells to be used to trigger temporal recovery of CREB-dependent transcriptional activity and endogenous gene expression under photolytic control.

Original language	English
Pages (from-to)	1813-1818
Number of pages	6
Journal	ACS Central Science
Volume	6
Issue number	10
Early online date	31 Aug 2020
DOIs	https://doi.org/10.1021/acscentsci.0c00736
Publication status	Published - 28 Oct 2020

Funding

We would like to thank Dr. Fuminori Sugihara (Osaka Univ.) for the use of a real-time PCR instrument. This research was supported by the following grants: Grant-in-Aid for Scientific Research (Grant 16K01933 and 20K05747 to M.M.; 25220207, 18H039351, and 19K22255 to K.K.); Innovative Areas “Frontier Research on Chemical Communications” (17H06409 to K.K.); “Brain Information Dynamics” (17H06312 to H.B.) of Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan; AMED (18he0902005h0004, 17ae0101041h9902, and 18fm0208018h0002 to K.K.); Takeda Science Foundation (to K.K. and H.B.); JSPS A3 Foresight Program; JSPS CORE-to-CORE Program “Asian Chemical Biology Initiative”; Japan (JSPS)-UK (RSC) Research Cooperative Program (JPJSBP120195705 to K.K.) and Royal Society International Exchange (IEC\R3\183068 to S.D.B.).

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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10.1021/acscentsci.0c00736

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abstract = "A novel photodeactivation strategy for controlling gene expression has been developed based on light-induced activation of cAMP response element binding protein (CREB). Light-induced cleavage of the photoresponsive protecting group of an antagonist of CREB binding protein (CBP) results in photocleaved products with weak binding affinity for CBP. This photodissociation reaction enables protein-protein interactions between CBP and CREB that trigger the formation of a multiprotein transcription complex to turn gene expression {"}on{"}. This enables irradiation of antagonist-treated HEK293T cells to be used to trigger temporal recovery of CREB-dependent transcriptional activity and endogenous gene expression under photolytic control.",

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AU - Bull, Steven D.

AU - Bito, Haruhiko

AU - Kikuchi, Kazuya

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A Photodeactivatable Antagonist for Controlling CREB-Dependent Gene Expression

Abstract

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