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- W4386987732 endingPage "105291" @default.
- W4386987732 startingPage "105291" @default.
- W4386987732 abstract "Impaired oxygen homeostasis is a frequently encountered pathophysiological factor in multiple complex diseases, including cardiovascular disease and cancer. While the canonical hypoxia response pathway is well characterised, less is known about the role of non-coding RNAs in this process. Here, we investigated the nascent and steady-state non-coding transcriptional responses in endothelial cells and their potential roles in regulating the hypoxic response. Notably, we identify a novel antisense long non-coding RNA that convergently overlaps the majority of the HIF1A locus, which is expressed across several cell types and elevated in atherosclerotic lesions. The antisense (HIF1A-AS) is produced as a stable, unspliced and polyadenylated nuclear retained transcript. HIF1A-AS is highly induced in hypoxia by both HIF1A and HIF2A and exhibits anticorrelation with the coding HIF1A transcript and protein expression. We further characterized this functional relationship by CRISPR-mediated bimodal perturbation of the HIF1A-AS promoter. We provide evidence that HIF1A-AS represses the expression of HIF1a in cis by repressing transcriptional elongation and deposition of H3K4me3, and that this mechanism is dependent on the act of antisense transcription itself. Overall, our results indicate a critical regulatory role of antisense mediated transcription in regulation of HIF1A expression and cellular response to hypoxia." @default.
- W4386987732 created "2023-09-24" @default.
- W4386987732 creator A5003292451 @default.
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- W4386987732 date "2023-09-01" @default.
- W4386987732 modified "2023-10-17" @default.
- W4386987732 title "Hypoxic regulation of hypoxia inducible factor 1 alpha via antisense transcription" @default.
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- W4386987732 doi "https://doi.org/10.1016/j.jbc.2023.105291" @default.