A Genetically Encoded FRET Probe to Detect Intranucleosomal Histone H3K9 or H3K14 Acetylation Using BRD4, a BET Family Member

Shiho Nakaoka, Kazuki Sasaki, Akihiro Ito, Yoichi Nakao, Minoru Yoshida

Research output: Contribution to journalArticle

12 Citations (Scopus)


Acetylation is a well-characterized histone modification, which plays important roles in controlling epigenetic gene expression, and its malfunction is tightly associated with cancer. By taking advantage of the specific binding of BRD4 to acetylated lysine residues, we developed a FRET-based probe for visualizing histone H3 acetylation in living cells. BRD4, a protein known to be involved in acute myeloid leukemia and nuclear protein in testis midline carcinoma, recognizes the acetylation of histone H3 via its bromodomains. The probe exhibited a significant change in FRET signaling that was dependent on histone H3 acetylation. Mutagenesis studies revealed that an increase in the emission ratio reflected the acetylation of either K9 or K14 of histone H3 within the probe. Since BRD4 has increasingly drawn attention as a new anticancer drug target, we demonstrated that the developed fluorescent probe will also serve as a powerful tool to evaluate BRD4 inhibitors in living cells.

Original languageEnglish
Pages (from-to)729-733
Number of pages5
JournalACS Chemical Biology
Issue number3
Publication statusPublished - 2016 Mar 18


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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