Reduce, Retain, Recycle: Mechanisms for Promoting Histone Protein Degradation versus Stability and Retention

Mol Cell Biol. 2021 May 21;41(6):e0000721. doi: 10.1128/MCB.00007-21. Epub 2021 May 21.


The eukaryotic genome is packaged into chromatin. The nucleosome, the basic unit of chromatin, is composed of DNA coiled around a histone octamer. Histones are among the longest-lived protein species in mammalian cells due to their thermodynamic stability and their associations with DNA and histone chaperones. Histone metabolism plays an integral role in homeostasis. While histones are largely stable, the degradation of histone proteins is necessary under specific conditions. Here, we review the physiological and cellular contexts that promote histone degradation. We describe specific known mechanisms that drive histone proteolysis. Finally, we discuss the importance of histone degradation and regulation of histone supply for organismal and cellular fitness.

Keywords: DNA replication; chaperone; chromatin; histone; nucleosome; nucleus; posttranslational modification; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cellular Senescence
  • DNA Replication
  • Histone Chaperones / metabolism
  • Histones / metabolism*
  • Humans
  • Protein Stability
  • Proteolysis


  • Histone Chaperones
  • Histones