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Epigenetic Control of Gene Expression by Lipid Metabolism
Author(s) -
Hirschey Matthew
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.415.1
Subject(s) - epigenetics , acetylation , histone , lipid metabolism , biology , gene expression , beta oxidation , metabolism , biochemistry , gene
Cells integrate nutrient sensing and metabolism to coordinate cellular growth. For example, glucose drives a gene expression program characterized by activating genes involved in its metabolism, in part, by increasing glucose‐derived histone acetylation. Here, we show that lipid‐derived acetyl‐CoA is also a major source of carbon for histone acetylation. Fatty acid oxidation leads to global cellular metabolic reprogramming and represses glucose and glutamine metabolism, thereby increasing intracellular lipid‐derived acetyl‐CoA. We traced 13C‐carbon from lipid onto histones, demonstrating that up to 90% of histone acetylation can be derived from fatty acid carbon. Gene expression profiling of octanoate‐treated hepatocytes identified genes involved in lipid metabolic processes are positively correlated. Conversely, cell cycle processes are negatively correlated, consistent with a suppression of proliferation upon lipid treatment. These studies uncover how fatty acid sensing and metabolism are integrated by epigenetic events that control gene expression, together ensuring proper cellular response to metabolites for growth. Support or Funding Information We would also like to acknowledge funding support from the American Heart Association 12SDG8840004 (to MDH), the National Institutes of Health (NIH) and the National Institute of Aging (NIA) grant R01AA022146 (to MDH), the Duke Pepper Older Americans Independence Center (OAIC) Program in Aging Research supported by the NIA (P30AG028716‐01), and the Duke Cancer Institute (P30CA014236). EM is supported by an NIH training grant to the Duke University Molecular Cancer Biology Training Program (5T32‐CA059365).Glucose‐derived carbon was previously considered the source of acetyl‐CoA for histone acetylation. Using a combination of proteomics and isotope tracing, we show that lipids are a major carbon source for histone acetylation. These studies expand the nutrient‐sensing landscape and uncover how lipid metabolism is integrated into epigenetic signaling.