RRC ID 34740
Author Ito T, Umehara T, Sasaki K, Nakamura Y, Nishino N, Terada T, Shirouzu M, Padmanabhan B, Yokoyama S, Ito A, Yoshida M.
Title Real-time imaging of histone H4K12-specific acetylation determines the modes of action of histone deacetylase and bromodomain inhibitors.
Journal Chem Biol
Abstract Histone acetylation constitutes an epigenetic mark for transcriptional regulation. Here we developed a fluorescent probe to visualize acetylation of histone H4 Lys12 (H4K12) in living cells using fluorescence resonance energy transfer (FRET) and the binding of the BRD2 bromodomain to acetylated H4K12. Using this probe designated as Histac-K12, we demonstrated that histone H4K12 acetylation is retained in mitosis and that some histone deacetylase (HDAC) inhibitors continue to inhibit cellular HDAC activity even after their removal from the culture. In addition, a small molecule that interferes with ability of the bromodomain to bind to acetylated H4K12 could be assessed using Histac-K12 in cells. Thus, Histac-K12 will serve as a powerful tool not only to understand the dynamics of H4K12-specific acetylation but also to characterize small molecules that modulate the acetylation or interaction status of histones.
Volume 18(4)
Pages 495-507
Published 2011-4-22
DOI 10.1016/j.chembiol.2011.02.009
PII S1074-5521(11)00078-0
PMID 21513886
MeSH Acetylation / drug effects Animals Binding Sites COS Cells Cell Survival Chlorocebus aethiops Chromosomes / drug effects Chromosomes / metabolism Drug Design Fluorescent Dyes / metabolism Histone Deacetylase Inhibitors / pharmacology* Histone Deacetylases / chemistry* Histone Deacetylases / genetics Histone Deacetylases / metabolism* Histones / chemistry* Histones / metabolism* Kinetics Lysine* Mitosis / drug effects Models, Molecular Molecular Imaging* Mutation Protein Structure, Tertiary / drug effects Substrate Specificity Time Factors Transcription, Genetic / drug effects
IF 5.915
Times Cited 65
DNA material Histac-K12 pcDNA3.1 (RDB12841)