Live-cell epigenome manipulation by synthetic histone acetylation catalyst system
-
- Yusuke Fujiwara
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan;
-
- Yuki Yamanashi
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan;
-
- Akiko Fujimura
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan;
-
- Yuko Sato
- Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan;
-
- Tomoya Kujirai
- Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0033, Japan
-
- Hitoshi Kurumizaka
- Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0033, Japan
-
- Hiroshi Kimura
- Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan;
-
- Kenzo Yamatsugu
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan;
-
- Shigehiro A. Kawashima
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan;
-
- Motomu Kanai
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan;
説明
<jats:title>Significance</jats:title> <jats:p>Chemical methods to install histone posttranslational modifications in live cells promise extraordinary potential in epigenome biology and medicine due to the use of endogenous protein levels and lack of genetic manipulation. In this study, we developed a chemical catalyst, PEG-LANA-DSSMe, that binds with nucleosome’s acidic patch and promotes regioselective, synthetic histone acetylation at H2BK120 in living cells. Importantly, the synthetic acetylation suppressed H2B ubiquitination, a critical epigenome mark in cell physiology. This achievement is an example of epigenome manipulation in living cells, entirely relying on the chemical system. In the long term, our catalyst system with further improvements may contribute to both therapy and elucidation of epigenetic mechanisms.</jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 118 (4), e2019554118-, 2021-01-19
Proceedings of the National Academy of Sciences
- Tweet
キーワード
- *catalyst
- Lysine/*chemistry/metabolism
- *histone
- Oligopeptides/chemistry
- *acetylation
- *epigenome
- Catalysis
- Epigenesis, Genetic
- Polyethylene Glycols
- Histones
- Epigenome
- Nucleosomes/chemistry/metabolism
- Humans
- Chemical Engineering/methods
- Lysine
- *Epigenome
- *ubiquitination
- Ubiquitination
- Acetylation
- Chemical Engineering
- Nucleosomes
- *Protein Processing, Post-Translational
- Histones/*chemistry/metabolism
- Glycoconjugates/*chemistry
- Physical Sciences
- Polyethylene Glycols/*chemistry
- Glycoconjugates
- Oligopeptides
- Protein Processing, Post-Translational
- HeLa Cells
詳細情報 詳細情報について
-
- CRID
- 1360009142749070976
-
- ISSN
- 10916490
- 00278424
-
- PubMed
- 33468653
-
- データソース種別
-
- Crossref
- KAKEN
- OpenAIRE