Journal
MOLECULAR NEUROBIOLOGY
Volume 57, Issue 12, Pages 4891-4910Publisher
SPRINGER
DOI: 10.1007/s12035-020-02057-3
Keywords
Fatty acid-binding protein (FABP); ATP-citrate lyase (ACLY); Acetyl-CoA; Histone acetylation; Caveolin-1; Astrocyte
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Funding
- Japan Society for the Promotion of Science (JSPS) KAKENHI Grant [15K16206, 17K15539, 20K11527, 16H05116, 19H04026]
- AMED [JP17dm0107071]
- GSK Japan Research Grant 2015
- Grants-in-Aid for Scientific Research [20K11527, 15K16206, 17K15539, 16H05116, 19H04026] Funding Source: KAKEN
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Fatty acid binding protein 7 (FABP7) is an intracellular fatty acid chaperon that is highly expressed in astrocytes, oligodendrocyte-precursor cells, and malignant glioma. Previously, we reported that FABP7 regulates the response to extracellular stimuli by controlling the expression of caveolin-1, an important component of lipid raft. Here, we explored the detailed mechanisms underlying FABP7 regulation of caveolin-1 expression using primary cultured FABP7-KO astrocytes as a model of loss of function and NIH-3T3 cells as a model of gain of function. We discovered that FABP7 interacts with ATP-citrate lyase (ACLY) and is important for acetyl-CoA metabolism in the nucleus. This interaction leads to epigenetic regulation of several genes, including caveolin-1. Our novel findings suggest that FABP7-ACLY modulation of nuclear acetyl-CoA has more influence on histone acetylation than cytoplasmic acetyl-CoA. The changes to histone structure may modify caveolae-related cell activity in astrocytes and tumors, including malignant glioma.
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