Macro domains as metabolite sensors on chromatin

Cell Mol Life Sci. 2013 May;70(9):1509-24. doi: 10.1007/s00018-013-1294-4. Epub 2013 Mar 3.


How metabolism and epigenetics are molecularly linked and regulate each other is poorly understood. In this review, we will discuss the role of direct metabolite-binding to chromatin components and modifiers as a possible regulatory mechanism. We will focus on globular macro domains, which are evolutionarily highly conserved protein folds that can recognize NAD(+)-derived metabolites. Macro domains are found in histone variants, histone modifiers, and a chromatin remodeler among other proteins. Here we summarize the macro domain-containing chromatin proteins and the enzymes that generate relevant metabolites. Focusing on the histone variant macroH2A, we further discuss possible implications of metabolite binding for chromatin function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Epigenesis, Genetic
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Models, Molecular
  • NAD / metabolism*
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Structure, Tertiary
  • Sirtuins / chemistry
  • Sirtuins / metabolism*


  • Chromatin
  • Histones
  • macroH2A histone
  • NAD
  • Poly(ADP-ribose) Polymerases
  • Sirtuins