Real-Time Imaging of Histone H4K12–Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors

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• 作者：Tamaki Ito¹ ; ³ ; Takashi Umehara⁴ ; Kazuki Sasaki¹ ; Yoshihiro Nakamura⁴ ; Norikazu Nishino⁵ ; Takaho Terada⁴ ; Mikako Shirouzu⁴ ; Balasundaram Padmanabhan⁴ ; Shigeyuki Yokoyama⁴ ; ⁶ ; Akihiro Ito¹ ; ² ; ⁷ ; ^{akihiro-i@riken.jp"" rel=""nofollow} ; Minoru Yoshida¹ ; ² ; ³ ; ⁷ ; ^{yoshidam@riken.jp"" rel=""nofollow}
• 刊名：Chemistry & Biology
• 出版年：2011
• 出版时间：22 April 2011
• 年：2011
• 卷：18
• 期：4
• 页码：495-507
• 全文大小：1284 K

文摘

Summary

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.