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

Beverley M. Dancy, Nicholas T. Crump, Daniel J. Peterson, Chandrani Mukherjee, Erin M. Bowers, Young Hoon Ahn, Minoru Yoshida, Jin Zhang, Louis C. Mahadevan, David J. Meyers, Jef D. Boeke, Philip A. Cole

    Research output: Contribution to journalArticlepeer-review

    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.

    Original languageEnglish (US)
    Pages (from-to)2113-2121
    Number of pages9
    JournalChemBioChem
    Volume13
    Issue number14
    DOIs
    StatePublished - Sep 24 2012

    Keywords

    • Drug design
    • Enzymes
    • FRET
    • Histone H4
    • Protein modifications

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Organic Chemistry

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