May 1, 2016
vine serum albumin (BSA), pH 7.4) and 100 ÎźL/well dispensed (Multidrop, Thermofisher) into white 96-well plates (Corning) followed by dispensing of test compounds from 10 mM stock solutions using an HP D300 Digital Dispenser (Hewlett-Packard). The LED-array was then placed on top of the 96-well plate and enzyme inhibitor solutions were exposed to light for 1 h (470 nm, 17 mW/cm2). Light exposure;vine serum albumin (BSA), pH 7.4) and 100 ÎźL/well dispensed (Multidrop, Thermofisher) into white 96-well plates (Corning) followed by dispensing of test compounds from 10 mM stock solutions using an HP D300 Digital Dispenser (Hewlett-Packard). The LED-array was then placed on top of the 96-well plate and enzyme inhibitor solutions were exposed to light for 1 h (470 nm, 17 mW/cm2). Light exposure
Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic processes have been implicated in the pathophysiology of multiple human diseases. Small-molecule inhibitors have been essential to advancing our understanding of the underlying molecular mechanisms of epigenetic processes. However, the resolution offered by small molecules is often insufficient to manipulate epigenetic processes with high spatiotemporal control. Here we present a generalizable approach, referred to as 'chemo-optical modulation of epigenetically regulated transcription' (COMET), enabling high-resolution, optical control of epigenetic mechanisms based on photochromic inhibitors of human histone deacetylases using visible light. COMET probes may be translated into new therapeutic strategies for diseases where conditional and selective epigenome modulation is required.
Reis, SA; Ghosh, B; Hendricks, JA; Szantai-Kis, DM; TĂśrk, L; Ross, KN; Lamb, J; Read-Button, W; Zheng, B; Wang, H; Salthouse, C; Haggarty, SJ; Mazitschek, R;
Journal: Nat. Chem. Biol. Pages: 317-323