同时进行单细胞蛋白质组学和表观遗传学分析,对人类细胞中素脱乙酶抑制的研究
1The University of Pittsburgh, Organ Pathobiology and Therapeutics Institute, Pittsburgh, PA, USA. orsburn@pitt.edu.
Communications biology
|December 30, 2025
概括
单细胞蛋白质组学在用基因素脱乙酶抑制剂治疗的癌细胞中发现了16种基因素修饰. 这种方法揭示了乙化异质性,为单个细胞提供了表型和表观遗传的见解.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 单细胞蛋白质组学通过质谱学 (SCP) 来量化单个细胞中的蛋白质.
- 高丰富的蛋白质,如染色质蛋白质,是SCP的合适目标.
- 基因组蛋白修饰在基因调节和癌症中起着至关重要的作用.
研究的目的:
- 应用SCP来分析癌细胞中的组素修饰.
- 为了研究mocetinostat的作用,一个基因素脱乙酶抑制剂,在基因素乙化.
- 为了探索单个癌细胞中的组素乙化位点的异质性.
主要方法:
- 通过质谱学 (SCP) 采用单细胞蛋白质组学.
- 癌细胞用mocetinostat进行治疗.
- 进行了翻译后修改 (PTM) 的识别和定位.
主要成果:
- 16个翻译后修饰 (PTM) 在单细胞中被识别并局部化,具有高位点特异性.
- 莫西丁诺斯塔特治疗诱导了基因素乙化位点的丰度和分布的异质性.
- 该研究证明了在单细胞中同时定量数百种蛋白质.
结论:
- 在单细胞中,SCP可以同时量化许多蛋白质和表观遗传修饰.
- 这种方法在单细胞水平上提供了表型和表观遗传的见解.
- 这些发现突显了SCP在癌症研究和理解药物反应方面的潜力.
相关概念视频
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...


