Nothing Is Yet Set in (Hi)stone: Novel Post-Translational Modifications Regulating Chromatin Function

Trends Biochem Sci. 2020 Oct;45(10):829-844. doi: 10.1016/j.tibs.2020.05.009. Epub 2020 Jun 1.


Histone post-translational modifications (PTMs) have emerged as exciting mechanisms of biological regulation, impacting pathways related to cancer, immunity, brain function, and more. Over the past decade alone, several histone PTMs have been discovered, including acylation, lipidation, monoaminylation, and glycation, many of which appear to have crucial roles in nucleosome stability and transcriptional regulation. In this review, we discuss novel histone PTMs identified within the past 10 years, with an extended focus on enzymatic versus nonenzymatic mechanisms underlying modification and adduction. Furthermore, we consider how these novel histone PTMs might fit within the framework of a so-called 'histone code', emphasizing the physiological relevance of these PTMs in metabolism, development, and disease states.

Keywords: acylation; glycation; histone code hypothesis; lipidation; monoaminylation; nonenzymatic adduction.

Publication types

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

MeSH terms

  • Acetylation
  • Chromatin / metabolism*
  • Gene Expression Regulation
  • Histones / metabolism*
  • Humans
  • Protein Processing, Post-Translational*


  • Chromatin
  • Histones