The common yet enigmatic activity of histone tail clipping

Histone proteolysis is sometimes described as an extreme posttranslational modification (PTM), as it removes both a stretch of histone sequence and any PTMs that were previously added to it. Such an acute and significant loss of information could trigger many different downstream effects, making it attractive as a mechanism for rapid gene silencing or activation. However, protease activity is challenging to study and is often treated like background noise that is best kept as low as possible. As both histones and protease activity are highly abundant in most cells, evidence of proteolysis of histone tails—a.k.a. histone clipping—has often been dismissed as nonspecific noise. Yet over the past decades there have been studies suggesting this activity should not be ignored, that it may represent a rare but relevant process with important roles in cell biology. Here, I review the key studies that both support this argument and raise additional questions about the mechanisms and functions of histone clipping.