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PMID: 19461003 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

ATP-citrate lyase links cellular metabolism to histone acetylation.

Science (New York, N.Y.) ·Vol. 324 ·No. 5930 ·2009-05-22 ·Pages 1076-80

Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB

Abstract

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.

MeSH Terms
3T3 Cells ATP Citrate (pro-S)-Lyase/genetics,metabolism Acetate-CoA Ligase/genetics,metabolism Acetyl Coenzyme A/metabolism Acetylation Adipocytes/cytology,metabolism Animals Cell Differentiation Cell Line Cell Line, Tumor Cell Nucleus/enzymology Cell Proliferation Citric Acid/metabolism Cytoplasm/enzymology Gene Expression Regulation Glucose/metabolism Glycolysis Histone Deacetylase Inhibitors Histone Deacetylases/metabolism Histones/metabolism Humans Intercellular Signaling Peptides and Proteins/metabolism Interleukin-3/metabolism Mice RNA Interference Transcription, Genetic
Chemicals
Histone Deacetylase Inhibitors Histones Intercellular Signaling Peptides and Proteins Interleukin-3 Citric Acid Acetyl Coenzyme A ATP Citrate (pro-S)-Lyase Histone Deacetylases Acetate-CoA Ligase Glucose
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wellen Kathryn E
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hatzivassiliou Georgia
Sachdeva Uma M
Bui Thi V
Cross Justin R
Thompson Craig B
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1164097
Published
2009-05-22
Pages
1076-80
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2746744
Subset
IM
Grants
NCI NIH HHS · R01 CA092660 · United States
NCI NIH HHS · R01 CA092660-09 · United States
NCI NIH HHS · R01 CA105463 · United States
NHLBI NIH HHS · T32-HL07439-27 · United States
Corrections
CommentIn
PMID: 19460991
External Links
PubMed source DOI: 10.1126/science.1164097 PMC Full Text View journal details
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