Live‐Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition |
| |
| Authors: | Beverley M Dancy Dr Nicholas T Crump Daniel J Peterson Dr Chandrani Mukherjee Dr Erin M Bowers Dr Young‐Hoon Ahn Dr Minoru Yoshida Dr Jin Zhang Dr Louis C Mahadevan Dr David J Meyers Dr Jef D Boeke Dr Philip A Cole |
| |
| Affiliation: | 1. Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 (USA);2. Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205 (USA);3. Nuclear Signalling Laboratory, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU (UK);4. Laboratory for Neurocognitive and Imaging Research, Kennedy Krieger Institute, 716 North Broadway, Baltimore, MD 21205 (USA);5. Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351‐0198 (Japan) |
| |
| Abstract: | Histone acetyltransferase enzymes (HATs) are important therapeutic targets, but there are few cell‐based assays available for evaluating the pharmacodynamics of HAT inhibitors. Here we present the application of a FRET‐based reporter, Histac, in live‐cell studies of p300/CBP HAT inhibition, by both genetic and pharmacologic disruption. shRNA knockdown of p300/CBP led to increased Histac FRET, thus suggesting a role for p300/CBP in the acetylation of the histone H4 tail. Additionally, we describe a new p300/CBP HAT inhibitor, C107, and show that it can also increase cellular Histac FRET. Taken together, these studies provide a live‐cell strategy for identifying and evaluating p300/CBP inhibitors. |
| |
| Keywords: | drug design enzymes FRET histone H4 protein modifications |
|
|
