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Energy stress-induced circEPB41(2) regulates lipogenesis through histone modifications [H3K9ac ChIP-seq]

ABSTRACT: The list of circular RNAs (circRNAs) involved in tumor metabolic reprogramming is rapidly increasing, but whether circRNAs have a role in linking epigenetic modification with lipid metabolism remains elusive. Here, we demonstrate that the circRNA circEPB41(2), which expression is driven by HNRNPA1 in response to glucose deprivation, is important for de novo lipogenesis. Moreover, we uncovered a genome-wide decrease in specific histone acetylation after circEPB41(2) depletion. These changes are associated with altered gene expression and observed cellular phenotypes, suggesting their functional significance. Mechanistically, we showed that circEPB41(2) regulates histone acetylation in part by modulating the stability and polyadenylation of SIRT6 through binding and maintaining the demethylase activity of FTO. Accordingly, circEPB41(2) silencing inhibited cellular lipid accumulation, suppressed cell proliferation, and inhibited cancer xenograft growth. Thus, circEPB41(2) may consider a target for cancer treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234822 | GEO | 2023/10/11

REPOSITORIES: GEO

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Energy stress-induced circEPB41(2) regulates lipogenesis through histone modifications [ncRNA-seq]

Project description:The list of circular RNAs (circRNAs) involved in tumor metabolic reprogramming is rapidly increasing, but whether circRNAs have a role in linking epigenetic modification with lipid metabolism remains elusive. Here, we demonstrate that the circRNA circEPB41(2), which expression is driven by HNRNPA1 in response to glucose deprivation, is important for de novo lipogenesis. Moreover, we uncovered a genome-wide decrease in specific histone acetylation after circEPB41(2) depletion. These changes are associated with altered gene expression and observed cellular phenotypes, suggesting their functional significance. Mechanistically, we showed that circEPB41(2) regulates histone acetylation in part by modulating the stability and polyadenylation of SIRT6 through binding and maintaining the demethylase activity of FTO. Accordingly, circEPB41(2) silencing inhibited cellular lipid accumulation, suppressed cell proliferation, and inhibited cancer xenograft growth. Thus, circEPB41(2) may consider a target for cancer treatment.

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Energy stress-induced circEPB41(2) regulates lipogenesis through histone modifications [RNA-seq]

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Project description:Acetylation and dimethylation of lysine 9 on histone H3 are prominent marks of euchromatin and heterochromatin, respectively. Moreover, histone acetylation has been linked to lipid metabolism. We have previously identified the transcription factor Cbf11 as a regulator of lipid metabolism and genome integrity in the fission yeast. Cut6, the acetyl-CoA carboxylase, is one of direct targets of Cbf11. To link the role of Cbf11 in lipid metabolism and chromatin regulation we have performed ChIP-seq of H3K9ac, H3K9me2 and H3 in WT and cbf11KO strains of Schizosaccharomyces pombe in three biological replicates. Strain genotypes: wild type JB32 (h+s); cbf11 knock-out MP44 (h+ cbf11::natR).

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