Genetically encoded system to track histone modification in vivo

Yuko Sato, Masanori Mukai, Jun Ueda, Michiko Muraki, Timothy J. Stasevich, Naoki Horikoshi, Tomoya Kujirai, Hiroaki Kita, Taisuke Kimura, Seiji Hira, Yasushi Okada, Yoko Hayashi-Takanaka, Chikashi Obuse, Hitoshi Kurumizaka, Atsuo Kawahara, Kazuo Yamagata, Naohito Nozaki, Hiroshi Kimura

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46 Citations (Scopus)

Abstract

Post-translational histone modifications play key roles in gene regulation, development, and differentiation, but their dynamics in living organisms remain almost completely unknown. To address this problem, we developed a genetically encoded system for tracking histone modifications by generating fluorescent modification-specific intracellular antibodies (mintbodies) that can be expressed in vivo. To demonstrate, an H3 lysine 9 acetylation specific mintbody (H3K9ac-mintbody) was engineered and stably expressed in human cells. In good agreement with the localization of its target acetylation, H3K9ac-mintbody was enriched in euchromatin, and its kinetics measurably changed upon treatment with a histone deacetylase inhibitor. We also generated transgenic fruit fly and zebrafish stably expressing H3K9ac-mintbody for in vivo tracking. Dramatic changes in H3K9ac-mintbody localization during Drosophila embryogenesis could highlight enhanced acetylation at the start of zygotic transcription around mitotic cycle 7. Together, this work demonstrates the broad potential of mintbody and lays the foundation for epigenetic analysis in vivo.

Original languageEnglish
Article number2436
JournalScientific Reports
Volume3
DOIs
Publication statusPublished - 2013

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Keywords

  • Chromatin Analysis
  • Fluorescent Proteins
  • Histone Posttranslational
  • Modifications
  • Subject Areas
  • Time-Lapse Imaging

ASJC Scopus subject areas

  • General

Cite this

Sato, Y., Mukai, M., Ueda, J., Muraki, M., Stasevich, T. J., Horikoshi, N., Kujirai, T., Kita, H., Kimura, T., Hira, S., Okada, Y., Hayashi-Takanaka, Y., Obuse, C., Kurumizaka, H., Kawahara, A., Yamagata, K., Nozaki, N., & Kimura, H. (2013). Genetically encoded system to track histone modification in vivo. Scientific Reports, 3, [2436]. https://doi.org/10.1038/srep02436