Histone cleavage as a mechanism for epigenetic regulation: current insights and perspectives

Discovered over a century ago, histones constitute one of the oldest families of proteins and have been remarkably conserved throughout eukaryotic evolution. However, only for the past 30 years have histones demonstrated that their influence extends far beyond packaging DNA. To create the various chromatin structures that are necessary for DNA function in higher eukaryotes, histones undergo posttranslational modifications. While many such modifications are well documented, others, such as histone tail cleavage are less understood. Recent studies have discovered several proteases that cleave histones and have suggested roles for clipped histones in stem cell differentiation and aging in addition to infection and inflammation; the underlying mechanisms, however, are uncertain. One histone class in particular, histone H3, has received outstanding interest due to its numerous N-terminal modification sites and prevalence in regulating homeostatic processes. Here, with special consideration of H3, we will discuss the novel findings regarding histone proteolytic cleavage as well as their significance in the studies of immunology and epigenetics.