German Cancer Research Center (DKFZ), Division of Proteomics of Stem Cells and Cancer, Heidelberg, Baden-Württemberg, Germany.
Medical Faculty, Heidelberg University, Heidelberg, Baden-Wurttemberg, Germany.
Proteomics. 2022 Aug;22(15-16):e2100206. doi: 10.1002/pmic.202100206. Epub 2022 Jun 6.
Chromatin is the assembly of genomic DNA and proteins packaged in the nucleus of eukaryotic cells, which together are crucial in regulating a plethora of cellular processes. Histones may be the best known class of protein constituents in chromatin, which are decorated by a range of post-translational modifications to recruit accessory proteins and protein complexes to execute specific functions, ranging from DNA compaction, repair, transcription, and duplication, all in a dynamic fashion and depending on the cellular state. The key role of chromatin in cellular fitness is emphasized by the deregulation of chromatin determinants predisposing to different diseases, including cancer. For this reason, deep investigation of chromatin composition is fundamental to better understand cellular physiology. Proteomic approaches have played a crucial role to understand critical aspects of this complex interplay, benefiting from the ability to identify and quantify proteins and their modifications in an unbiased manner. This review gives an overview of the proteomic approaches that have been developed by combining mass spectrometry-based with tailored biochemical and genetic methods to examine overall protein make-up of chromatin, to characterize chromatin domains, to determine protein interactions, and to decipher the broad spectrum of histone modifications that represent the quintessence of chromatin function.
染色质是真核细胞细胞核中基因组 DNA 和蛋白质的组装体，对于调节众多细胞过程至关重要。组蛋白可能是染色质中最著名的一类蛋白质成分，它们通过一系列翻译后修饰来招募辅助蛋白和蛋白复合物，以执行特定的功能，从 DNA 紧缩、修复、转录和复制，所有这些都是动态的，并取决于细胞状态。染色质在细胞适应性中的关键作用，通过染色质决定因素的失调来强调，这些决定因素易导致包括癌症在内的多种疾病。出于这个原因，深入研究染色质组成对于更好地理解细胞生理学至关重要。蛋白质组学方法在理解这一复杂相互作用的关键方面发挥了至关重要的作用，得益于以无偏倚的方式识别和定量蛋白质及其修饰的能力。这篇综述概述了蛋白质组学方法，这些方法通过将基于质谱的方法与定制的生化和遗传方法相结合，用于检查染色质的整体蛋白质组成、描述染色质结构域、确定蛋白质相互作用以及解析代表染色质功能本质的广泛组蛋白修饰。
