A Photodeactivatable Antagonist for Controlling CREB-Dependent Gene Expression

[Image: see text] 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.