ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation

See allHide authors and affiliations

Science  22 May 2009:
Vol. 324, Issue 5930, pp. 1076-1080
DOI: 10.1126/science.1164097

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


Histone acetylation in single-cell eukaryotes relies on acetyl coenzyme A (acetyl-CoA) synthetase enzymes that use acetate to produce acetyl-CoA. Metazoans, however, use glucose as their main carbon source and have exposure only to low concentrations of extracellular acetate. We have shown that histone acetylation in mammalian cells is dependent on adenosine triphosphate (ATP)–citrate lyase (ACL), the enzyme that converts glucose-derived citrate into acetyl-CoA. We found that ACL is required for increases in histone acetylation in response to growth factor stimulation and during differentiation, and that glucose availability can affect histone acetylation in an ACL-dependent manner. Together, these findings suggest that ACL activity is required to link growth factor–induced increases in nutrient metabolism to the regulation of histone acetylation and gene expression.

  • * These authors contributed equally to this work.

  • Present address: Genentech Inc., South San Francisco, CA 94080, USA.

View Full Text

Stay Connected to Science