Live‐Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition

Beverley M. Dancy(Johns Hopkins University), Nicholas T. Crump(University of Oxford), Daniel J. Peterson(Kennedy Krieger Institute), Chandrani Mukherjee(Johns Hopkins University), Erin M. Bowers(Johns Hopkins University), Young‐Hoon Ahn(Johns Hopkins University), Minoru Yoshida(RIKEN Advanced Science Institute), Jin Zhang(Johns Hopkins University), Louis C. Mahadevan(University of Oxford), David J. Meyers(Johns Hopkins University), Jef D. Boeke(Johns Hopkins University), Philip A. Cole(Johns Hopkins University)
ChemBioChem
September 7, 2012
10.1002/cbic.201200381
Cited by 50

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.

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