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一个活细胞表观基因组操纵由光刺激响应的质甲基转移酶抑制剂

Chuan-Shuo Wu^1,2, Xin Sun^1,2, Li Liu^1,2

¹Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|September 9, 2024

概括

科学家们开发了一种光激活的抑制剂,用于控制活细胞中素二甲基化 (H3K9me2). 这种新工具为表观基因组操纵和治疗应用提供了精确的时空控制.

科学领域:

表观遗传学和分子生物学
化学生物学化学生物学
染色体规则染色体规则染色体规则

背景情况:

基因组转化后修饰 (PTMs) 对于调节基因表达和染色体结构至关重要.
目前用于基因素修饰的方法缺乏时空控制或不适合原生染色素.
精确控制活细胞中组织素甲基化仍然是一个重大挑战.

研究的目的:

在活细胞中开发一种用于空间时空操纵素二甲基化 (H3K9me2) 的新方法.
创建一个针对G9a甲基转移酶的光响应抑制剂,以对H3K9me2.2进行按需控制.
为了解表观遗传学和探索治疗应用提供一个工具.

主要方法:

一种针对G9a甲基转移酶的光抑制剂的设计和合成.
在体外评估抑制剂的稳定性,光激活和G9a抑制.
在暴露于光线后,评估抑制剂在活细胞中抑制H3K9me2的有效性.

主要成果:

摄影中的分子在生理条件下表现出稳定性,在暴露于光线时迅速激活.
活性抑制剂在体外有效抑制了G9a甲基转移酶的活性.
该系统成功地降低了活细胞中的H3K9me2水平,并进行了时间控制.

结论:

一个新的可光激活的化学系统能够精确地控制活细胞中素二甲基化 (H3K9me2).
该工具为研究表观遗传学和开发基于表观基因组的疗法提供了有价值的方法.
这种方法提供了前所未有的控制内源性组织组织蛋白修饰的方法.

关键词:

化学调制是一种化学调制.基质子的修改基质子的修改溶氨酸甲基化溶氨酸甲基化氨酸甲基转移酶是什么照片响应式的照片响应式

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