In conclusion, we emphasize the significance of reviving the study of histone proteolysis both from a biological and an experimental perspective. Finally, unanticipated histone proteolysis has probably left a mark on many studies of histones in the past. Given the importance of histone modifications in epigenetic regulation we further elaborate on the different ways in which histone proteolysis could play a role in epigenetics. However, the authors often not clearly distinguish or determine whether degradation or clipping was studied. Since the first report decades ago, proteolysis has been found in a broad spectrum of eukaryotic organisms.

Our initial observation is that these two different classes are very hard to distinguish both experimentally and biologically, because they can both be mediated by the same enzymes. We propose for the first time to divide histone proteolysis into “histone degradation” and the epigenetically connoted “histone clipping”.

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