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Mass spectrometry has played a vital role in defining what we understand about mechanisms regulating chromatin structure and function. With the speed, sensitivity and resolution of new generation mass spectrometers, researchers are now well-positioned to not only analyze bulk chromatin features, but to also begin to explore lower abundance chromatin signatures that help define the detailed epigenetic landscape of a chromosome. The components of chromatin that have been the primary focus of analysis by mass spectrometry are proteins and protein posttranslational modifications (PTMs). Below I discuss each of these components and provide insight into how mass spectrometry is helping to reshape how we study epigenetic mechanisms.