Spatiotemporal Control of Acetyl-CoA Metabolism in Chromatin Regulation

Trends Biochem Sci. 2018 Jan;43(1):61-74. doi: 10.1016/j.tibs.2017.11.004. Epub 2017 Nov 23.


The epigenome is sensitive to the availability of metabolites that serve as substrates of chromatin-modifying enzymes. Links between acetyl-CoA metabolism, histone acetylation, and gene regulation have been documented, although how specificity in gene regulation is achieved by a metabolite has been challenging to answer. Recent studies suggest that acetyl-CoA metabolism is tightly regulated both spatially and temporally to elicit responses to nutrient availability and signaling cues. Here we discuss evidence that acetyl-CoA production is differentially regulated in the nucleus and cytosol of mammalian cells. Recent findings indicate that acetyl-CoA availability for site-specific histone acetylation is influenced through post-translational modification of acetyl-CoA-producing enzymes, as well as through dynamic regulation of the nuclear localization and chromatin recruitment of these enzymes.

Keywords: acetyl-CoA; acetylation; compartmentalization; epigenetics; metabolism.

Publication types

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

MeSH terms

  • Acetyl Coenzyme A / metabolism*
  • Animals
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Chromatin / genetics*
  • Chromatin / metabolism*
  • Cytosol / metabolism
  • Humans


  • Chromatin
  • Acetyl Coenzyme A