表观遗传学特征的综合活性，包括组蛋白翻译后修饰、DNA甲基化和核小体定位，独立于DNA序列的变化调控基因表达，定义了一个生物体的共享遗传信息如何用于产生不同细胞表型。表观遗传过程的改变与多种疾病（包括癌症）相关联，从而加强了对以写入、擦除或读取组蛋白和DNA修饰的蛋白质为靶点的药物发现的兴趣。基于质谱（MS）的蛋白质组学已经成为一种多功能工具，可以在药物发现流程中协助目标验证、目标解析和体内监测药物疗效。在这里，我们概述了基于质谱的蛋白质组学在表观遗传药物发现中的贡献，描述了可以用来支持不同药物发现流程的主要方法，并突出了它们对表观遗传药物的开发和表征的贡献。©2023年作者。由Wiley-VCH GmbH出版的蛋白质组学杂志发表。

The combined activity of epigenetic features, which include histone post-translational modifications, DNA methylation, and nucleosome positioning, regulates gene expression independently from changes in the DNA sequence, defining how the shared genetic information of an organism is used to generate different cell phenotypes. Alterations in epigenetic processes have been linked with a multitude of diseases, including cancer, fueling interest in the discovery of drugs targeting the proteins responsible for writing, erasing, or reading histone and DNA modifications. Mass spectrometry (MS)-based proteomics has emerged as a versatile tool that can assist drug discovery pipelines from target validation, through target deconvolution, to monitoring drug efficacy in vivo. Here, we provide an overview of the contributions of MS-based proteomics to epigenetic drug discovery, describing the main approaches that can be used to support different drug discovery pipelines and highlighting how they contributed to the development and characterization of epigenetic drugs.© 2023 The Authors. Proteomics published by Wiley-VCH GmbH.