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Fasting-induced JMJD3 histone demethylase epigenetically activates mitochondrial fattyacid beta-oxidation

ABSTRACT: Jumonji D3 (JMJD3) histone demethylase epigenetically regulates development, differentiation, and immunity by demethylating a gene-repression histone mark, H3K27-me3, but a role for JMJD3 in metabolic regulation has not been described. SIRT1 deacetylase maintains energy balance during fasting by directly activating both hepatic gluconeogenic and mitochondrial fatty acid beta-oxidation genes, but the underlying epigenetic and gene-specific mechanisms remain unclear. To explore global hepatic functions of JMJD3, mRNA levels in control and JMJD3-downregulated hepatocytes were compared by RNA-seq analysis. Expression of 2,772 and 2,143 genes was significantly decreased and increased, respectively, over 1.5-fold, by downregulation of JMJD3. ). In gene ontology analysis, genes downregulated with the highest significance were those involved in mitochondrial functions, particularly oxidation/reduction, the respiratory chain, and fatty acid beta-oxidation, Overall, in this study, JMJD3 was shown unexpectedly to be a gene-specific transcriptional partner of SIRT1 and these epigenetic factors interact with the nuclear receptor PPARalpha to epigenetically activate mitochondrial beta-oxidation, but not gluconeogenic, genes during fasting.

ORGANISM(S): Mus musculus

PROVIDER: GSE113032 | GEO | 2018/04/14

REPOSITORIES: GEO

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