Histone acetylation is dynamically and reversibly controlled by histone acetyltransferases and deacetylases during cellular events such as cell division and differentiation. However, the dynamics of histone modifications in living cells are poorly understood because of the lack of experimental tools to monitor them in a real-time fashion. Herein, we introduce Förster/fluorescence resonance energy transfer (FRET)-based indicators to visualize acetylation of histone H4, and describe a protocol for live-cell imaging with high spatiotemporal resolution. © 2014 Springer Science+Business Media, LLC.