Transcriptomics

Dataset Information

0

Mitochondrial fatty acid oxidation regulates monocytic type I interferon signaling via histone acetylation.


ABSTRACT: Although lipid-derived acetyl-CoA is a major carbon source for histone acetylation, the contribution of fatty acid -oxidation (FAO) to this process remains poorly characterized. To investigate this, we generated mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1, distal FAO enzyme) knockout macrophages. 13C-carbon tracing confirmed reduced FA-derived carbon incorporation into histone H3 and RNA-seq identified diminished interferon stimulated gene expression in the absence of ACAT1. Chromatin accessibility at Stat1 locus was diminished in ACAT1-/- cells. CHIP analysis demonstrated reduced acetyl-H3 binding to Stat1 promoter/enhancer regions and increasing histone acetylation rescued Stat1 expression. IFNβ release was blunted in ACAT1-/- and recovered by ACAT1 reconstitution. Furthermore, ACAT1-dependent histone acetylation required an intact acetylcarnitine shuttle. Finally, obese subjects’ monocytes exhibited increased ACAT1 and histone acetylation levels. Thus, our study identifies a novel link between FAO-mediated epigenetic control of type 1 interferon signaling and uncovers a potential mechanistic link between obesity and type I inferon signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE279878 | GEO | 2025/01/07

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2017-05-01 | E-GEOD-76850 | biostudies-arrayexpress
2017-09-25 | GSE79524 | GEO
2017-02-13 | GSE71230 | GEO
2022-01-06 | GSE178160 | GEO
2022-01-06 | GSE178159 | GEO
2025-03-17 | GSE291785 | GEO
2023-05-24 | E-MTAB-11082 | biostudies-arrayexpress
2021-11-03 | E-MTAB-11081 | biostudies-arrayexpress
2017-05-01 | E-GEOD-76853 | biostudies-arrayexpress
2011-05-19 | E-GEOD-28734 | biostudies-arrayexpress