2018年6月13日
Biomimetic Artificial Epigenetic Code for Targeted Acetylation of Histones
Journal of the American Chemical Society
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- 巻
- 140
- 号
- 23
- 開始ページ
- 7108
- 終了ページ
- 7115
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/jacs.8b01518
- 出版者・発行元
- American Chemical Society
While the central role of locus-specific acetylation of histone proteins in eukaryotic gene expression is well established, the availability of designer tools to regulate acetylation at particular nucleosome sites remains limited. Here, we develop a unique strategy to introduce acetylation by constructing a bifunctional molecule designated Bi-PIP. Bi-PIP has a P300/CBP-selective bromodomain inhibitor (Bi) as a P300/CBP recruiter and a pyrrole-imidazole polyamide (PIP) as a sequence-selective DNA binder. Biochemical assays verified that Bi-PIPs recruit P300 to the nucleosomes having their target DNA sequences and extensively accelerate acetylation. Bi-PIPs also activated transcription of genes that have corresponding cognate DNA sequences inside living cells. Our results demonstrate that Bi-PIPs could act as a synthetic programmable histone code of acetylation, which emulates the bromodomain-mediated natural propagation system of histone acetylation to activate gene expression in a sequence-selective manner.
- ID情報
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- DOI : 10.1021/jacs.8b01518
- ISSN : 1520-5126
- ISSN : 0002-7863
- PubMed ID : 29792694
- SCOPUS ID : 85048743029