ATP-citrate lyase links cellular metabolism to histone acetylation.
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.
Wellen
Kathryn E
KE
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hatzivassiliou
Georgia
G
Sachdeva
Uma M
UM
Bui
Thi V
TV
Cross
Justin R
JR
Thompson
Craig B
CB
D016475:3T3 Cells; D001275:ATP Citrate (pro-S)-Lyase / Q000235:genetics / Q000378:metabolism*; D000106:Acetate-CoA Ligase / Q000235:genetics / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D049109:Cell Proliferation; D019343:Citric Acid / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D051379:Mice; D034622:RNA Interference; D014158:Transcription, Genetic
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D007377:Interleukin-3; D019343:Citric Acid; D000105:Acetyl Coenzyme A; D001275:ATP Citrate (pro-S)-Lyase; D006655:Histone Deacetylases; D000106:Acetate-CoA Ligase; D005947:Glucose