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

Research output: Contribution to journalArticlepeer-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 languageEnglish
Pages (from-to)1813-1818
Number of pages6
JournalACS Central Science
Volume6
Issue number10
Early online date31 Aug 2020
DOIs
Publication statusPublished - 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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