biostudies-literatureNonomura TJapan Agency for Medical Research and DevelopmentPrecursory Research for Embryonic Science and TechnologyJapan Society for the Promotion of Sciencee202416420https://www.ebi.ac.uk/biostudies/studies/S-EPMC11753602biostudies-literatureUnknown64(4)Optical regulation of transcription using chemical compounds is an effective strategy to manipulate gene expression spatiotemporally. Conventional caging approaches with photoremovable protecting groups may require intense UV-light exposure and release potentially toxic byproducts. To address these problems, here we developed a light-mediated transcriptional regulation system by combining a caging-group-free photoactivatable dye PaX₅₆₀ and a multidrug-binding transcriptional regulator QacR. The cationic dye generated from PaX₅₆₀ through traceless photoconversion bound QacR and reduced its repressor function, resulting in transcriptional activation. Importantly, this system allowed transcriptional activation with a large dynamic range under mild visible light exposure and simultaneous detection of the state of the photoactivated effector. This module was integrated into the T7 RNA polymerase expression system to demonstrate light-activated transcription in vitro and in living cells.Angewandte Chemie (International ed. in English)Light-Activated Gene Expression System Using a Caging-Group-Free Photoactivatable Dye.PMC11753602JPMJPR22ECJP24ama121054JP22H05425JP23H04880, JP23H04881, JP21H04706, JP23KK0106, JP24H00494Nonomura TMinoshima MKikuchi KfalseLight-Activated Gene Expression System Using a Caging-Group-Free Photoactivatable Dye.Optical regulation of transcription using chemical compounds is an effective strategy to manipulate gene expression spatiotemporally. Conventional caging approaches with photoremovable protecting groups may require intense UV-light exposure and release potentially toxic byproducts. To address these problems, here we developed a light-mediated transcriptional regulation system by combining a caging-group-free photoactivatable dye PaX₅₆₀ and a multidrug-binding transcriptional regulator QacR. The cationic dye generated from PaX₅₆₀ through traceless photoconversion bound QacR and reduced its repressor function, resulting in transcriptional activation. Importantly, this system allowed transcriptional activation with a large dynamic range under mild visible light exposure and simultaneous detection of the state of the photoactivated effector. This module was integrated into the T7 RNA polymerase expression system to demonstrate light-activated transcription in vitro and in living cells.2025-01-01T00:00:00Z2025 Jan2025-04-18T12:46:27.231Z2025-04-06T22:07:21.611ZS-EPMC117536023944419010.1002/anie.202416420