Chromatin Regulation through Ubiquitin and Ubiquitin-like Histone Modifications

Trends Biochem Sci. 2021 Apr;46(4):258-269. doi: 10.1016/j.tibs.2020.11.005. Epub 2020 Dec 9.


Chromatin functions are influenced by the addition, removal, and recognition of histone post-translational modifications (PTMs). Ubiquitin and ubiquitin-like (UBL) PTMs on histone proteins can function as signaling molecules by mediating protein-protein interactions. Fueled by the identification of novel ubiquitin and UBL sites and the characterization of the writers, erasers, and readers, the breadth of chromatin functions associated with ubiquitin signaling is emerging. Here, we highlight recently appreciated roles for histone ubiquitination in DNA methylation control, PTM crosstalk, nucleosome structure, and phase separation. We also discuss the expanding diversity and functions associated with histone UBL modifications. We conclude with a look toward the future and pose key questions that will drive continued discovery at the interface of epigenetics and ubiquitin signaling.

Keywords: DNA methylation; epigenetics; histones; phase separation; post-translational modifications; ubiquitin-like modifications; ubiquitination.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Chromatin*
  • Histone Code*
  • Histones / metabolism
  • Protein Processing, Post-Translational
  • Ubiquitin / metabolism


  • Chromatin
  • Histones
  • Ubiquitin