Live-cell studies of p300/CBP histone acetyltransferase activity and inhibition.

Journal article

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.

Authors: Dancy, B; Crump, N; Peterson, D; Mukherjee, C; Bowers, E

• Publication status: Published
• Journal: Chembiochem : a European journal of chemical biology
• Volume: 13
• Issue: 14
• Pages: 2113-2121
• Publication date: 2012-09-01
• DOI: 10.1002/cbic.201200381
• EISSN: 1439-7633
• ISSN: 1439-4227
• Language: English
• Keywords: RNA Interference; p300-CBP Transcription Factors; Animals; Fluorescence Resonance Energy Transfer; Cercopithecus aethiops; COS Cells; Recombinant Proteins; Enzyme Inhibitors; Cell Survival; RNA, Small Interfering; Acetylation