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Energy stress-induced circEPB41(2) regulates lipogenesis through histone modifications [ncRNA-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: GSE272595 | GEO | 2024/07/25

REPOSITORIES: GEO

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

2023-10-11 | GSE234823 | GEO

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

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Project description:Sirt6, the NAD+-dependent deacetylase, has been described to deacetylate H3K9, H3K18, and H3K56. However, analysis of the acetylation status revealed that loss of Sirt6 caused a massive increase of histone H3K56ac levels but no detectable change of histone H3K9ac and H3K18ac, indicating that SIRT6 is the dominant deacetylase for H3K56ac in muscle stem cells (MuSCs). Further, we investigate genome-wide H3K56ac profiling in the absence of Sirt6 in MuSCs and mouse embryonic stem cells (mESCs) using high throughput sequencing (ChIP-seq).

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Genome-wide H3K56ac profiling after Sirt6 inactivation in MuSCs [ChIP-seq]

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