Karl F Poncha, Alyssa T Paparella, Nicolas L Young
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引用次数: 0
Abstract
Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM analysis and highlight the advantages of mass spectrometry techniques in providing comprehensive and quantitative insights into histone proteoforms. Key considerations in experimental design, sample preparation, chromatographic separation, and data analysis are outlined for the effective application of mass spectrometry for histone proteoform studies. By integrating these technological advancements on the side of sample preparation, instrumentation, and data processing a deeper understanding of chromatin regulation through PTM crosstalk is achieved, paving the way for mass spectrometry-based proteomics to spearhead the discovery of novel therapeutic strategies with proteoform level specificity.
期刊介绍:
The aim of the journal Mass Spectrometry Reviews is to publish well-written reviews in selected topics in the various sub-fields of mass spectrometry as a means to summarize the research that has been performed in that area, to focus attention of other researchers, to critically review the published material, and to stimulate further research in that area.
The scope of the published reviews include, but are not limited to topics, such as theoretical treatments, instrumental design, ionization methods, analyzers, detectors, application to the qualitative and quantitative analysis of various compounds or elements, basic ion chemistry and structure studies, ion energetic studies, and studies on biomolecules, polymers, etc.