Successful tracking of histone acetylation, a major player in gene activation
A step in the development of anti-cancer drugs
Under the leadership of SATO Yuko (Specially Appointed Researcher) and KIMURA Hiroshi (Associate Professor, Graduate School of Frontier Biosciences, Osaka University) a group of researchers developed technology for detecting post-translational histone modifications such as acetylation.
Heretofore, it has not been possible to observe post-translational modifications of proteins. This group made mintbodies ( m odification specific int racellular anti body ), based on antibodies, to specifically recognize modified histone H3. They then inserted them into fruit flies and zebrafish in their early development.
This group observed acetylation as a post-translational modification for the first time, meaning that live-cell imaging becomes possible. It is expected that mintbodies will be very useful in generation and regeneration research and in the development of drugs for cancer and other conditions.
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.
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To learn more about this research, please read the full research report entitled " Genetically encoded system to track histone modification in vivo " at this page of the Scientific Reports website.
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