Chromatin is unevenly distributed within the eukaryote nucleus and it contributes
to the formation of morphologically and functionally distinct substructures, called
chromatin domains and nuclear bodies. Here we describe an approach to assess specific
chromatin features, the histone posttranslational modifications (PTMs), of the largest
nuclear sub-compartment, the nucleolus. In this chapter, methods for the isolation
of nucleolus-associated chromatin from native or formaldehyde-fixed cells and the
effect of experimental procedures on the outcome of mass spectrometry analysis of
histone PTMs are compared.