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 hist...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2009-05, Vol.324 (5930), p.1076-1080
Main Authors: Wellen, Kathryn E, Hatzivassiliou, Georgia, Sachdeva, Uma M, Bui, Thi V, Cross, Justin R, Thompson, Craig B
Format: Article
Language:English
Subjects:
3T3 Cells
Acetate-CoA Ligase - genetics
Acetate-CoA Ligase - metabolism
Acetates
Acetyl Coenzyme A - metabolism
Acetylation
Adipocytes
Adipocytes - cytology
Adipocytes - metabolism
Animals
ATP Citrate (pro-S)-Lyase - genetics
ATP Citrate (pro-S)-Lyase - metabolism
Biochemistry
Biological and medical sciences
Cell Differentiation
Cell Line
Cell Line, Tumor
Cell lines
Cell metabolism, cell oxidation
Cell Nucleus - enzymology
Cell physiology
Cell Proliferation
Cellular biology
Cellular differentiation
Cellular metabolism
Chromatin
Citric Acid - metabolism
Cytoplasm - enzymology
Enzymes
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Glucose
Glucose - metabolism
Glycolysis
HCT116 cells
Histone Deacetylase Inhibitors
Histone Deacetylases - metabolism
Histones
Histones - metabolism
Humans
Intercellular Signaling Peptides and Proteins - metabolism
Interleukin-3 - metabolism
Metabolism
Metazoa
Mice
Molecular and cellular biology
RNA Interference
Small interfering RNA
Transcription, Genetic
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1164097