Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover-the complete loss of old, and replacement by new, nucleosomal histones-is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues. Here, we discuss both past and present proteomic methods (eg, mass spectrometry, human "bomb pulse labeling") for investigating histone turnover in brain with the hope that such information may stimulate future investigations of both adaptive and aberrant forms of "neuroepigenetic" plasticity.

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