合成后翻译性修饰:化学催化剂驱动的原生染色体的区域选择性基离合
Yoshifumi Amamoto1,2, Yuki Aoi1,2, Nozomu Nagashima1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|May 24, 2017
概括
研究人员开发了一种合成催化剂 (DSH) 来精确修改基因组,使得对基因调节和疾病的新见解成为可能. 这种方法允许本地染色体的特定基因组转化后修饰 (PTM).
科学领域:
- 表观遗传学和分子生物学
- 染色体生物学
- 化学生物学
背景情况:
- 基因转录后修饰 (PTM) 对于基因转录调节至关重要.
- 失调的PTM与癌症等疾病有关.
- 目前的方法缺乏在复杂的基因组网络中研究PTM的选择性.
研究的目的:
- 开发一种用于本地染色体选择性修饰的新方法.
- 研究特定基因组PTM在染色体结构和基因调节中的功能作用.
主要方法:
- 一种合成催化剂DMAP-SH (DSH) 在生理条件下被开发来激活.
- 为了有针对性的输送,DSH与核体配体 (例如LANA- ) 结合.
- 用DSH结合物将自然和非自然的PTM引入复合和原生染色体中的基因组.
主要成果:
- 在特定的氨酸残留物中,DSH成功地促进了各种PTM (乙化,化,无化,化和化标记).
- 使用LANA-DSH实现了基因组H2B lysine-120 (K120) 的化.
- 通过减少核细胞间相互作用,K120乙化和化调节了高阶染色体结构.
结论:
- 通过DSH催化剂,可以在原生染色体中进行选择性质PTM,从而克服了先前的方法限制.
- 这种方法有助于研究个别的PTM及其在PTM网络中的作用.
- 这种方法为剖析染色体调节机制和了解疾病的发病提供了多方面的应用.
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