Hypoxia exposure and methylation
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PROVIDER: PRJNA682379 | ENA |
REPOSITORIES: ENA
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Project description:Paternal hypoxia exposure primes offspring for increased hypoxia resistance
| PRJNA673886 | ENA
Project description:Environmental challenges experienced by an organism can have multiple effects at an individual level, with recent work also suggesting these challenges may affect their unexposed offspring. In a time of rapid environmental change, understanding whether environmental challenges experienced by organisms could increase the fitness of future generations to survive these same stressors, is critically needed. Low dissolved oxygen is a common environmental challenge that aquatic organisms encounter, resulting in numerous physiological, phenotypic, and epigenetic changes. In this study, we use zebrafish (Danio rerio) as a model to investigate how paternal hypoxia experience impacts subsequent progeny. Males were exposed to moderate hypoxia (11-13 kPA) for 2 weeks, bred to create an F1 generation, and progeny underwent an acute hypoxia (0-1 kPA) tolerance assay. Using time to loss of equilibrium and loss of equilibrium frequency as measured of hypoxia resistance, we show that paternal exposure to hypoxia endow offspring with a greater tolerance to acute hypoxia, compared to offspring of unexposed males, though there are strong family x treatment effects. In addition to phenotypic alternations, we also investigated changes in gene expression in offspring. We conducted RNA-Seq on whole fry and detected 91 differentially expressed genes, including two hemoglobin genes that are significantly upregulated by more than 4-fold in the offspring of hypoxia exposed males. Moreover, the offspring which maintained equilibrium the longest showed the greatest upregulation in hemoglobin expression. Paternal exposures to physiological challenges are thus able to impact the phenotype and gene expression of their unexposed progeny. We conducted whole genome bisulfite sequencing (WGBS) on the sperm of parental males to assess whether changes in progeny phenotype and gene expression are underpinned by changes in DNA methylation. While we observed coupling of methylation levels in the parental sperm and gene expression in progeny overall, we did not detect differential methylation at any of the differentially expressed genes, suggesting that another epigenetic mechanism is responsible for the observed changes in gene expression. Overall, our findings suggest that a ‘memory’ of past hypoxia exposure is maintained and that this environmentally induced information is transferred to subsequent generations, pre-acclimating progeny to cope with hypoxic conditions.
2022-01-01 | GSE160662 | GEO
Project description:Individuals with various high-altitude exposures have been recruited in this study to research the effects of differential exposure to high altitude on the epigenome
2020-12-04 | GSE162606 | GEO
Project description:Hypoxia is a physiological stress that frequently occurs in solid tissues. Autophagy, a ubiquitous degradation/recycling system in eukaryotic cells, renders cells tolerant to multiple stressors. However, the mechanisms underlying autophagy initiation upon hypoxia remains unclear. This study identifies an oxygen-sensitive methylation of ULK1 with an important role in hypoxic stress adaptation by promoting autophagy induction.
2022-01-25 | PXD031209 |
Project description:Hypoxia has profound and diverse effects on aerobic organisms, disrupting oxidative phosphorylation and activating several protective pathways. Predictions have been made that exposure to mild intermittent hypoxia may be protective against more severe exposure and may extend lifespan. Here we report the lifespan effects of chronic, mild, intermittent hypoxia and short-term survival in acute severe hypoxia in four clones of Daphnia magna originating from either permanent or intermittent habitats. We test the hypothesis that acclimation to chronic mild intermittent hypoxia can extend lifespan through activation of antioxidant and stress-tolerance pathways and increase survival in acute severe hypoxia through activation of oxygen transport and storage proteins and adjustment to carbohydrate metabolism. Unexpectedly, we show that chronic hypoxia extended the lifespan in the two clones originating from intermittent habitats but had the opposite effect in the two clones from permanent habitats, which also showed lower tolerance to acute hypoxia. Exposure to chronic hypoxia did not protect against acute hypoxia; to the contrary, Daphnia from the chronic hypoxia treatment had lower acute hypoxia tolerance than normoxic controls. Few transcripts changed their abundance in response to the chronic hypoxia treatment in any of the clones. After 12 hours of acute hypoxia treatment, the transcriptional response was more pronounced, with numerous protein-coding genes with functionality in oxygen transport, mitochondrial and respiratory metabolism, and gluconeogenesis, showing up-regulation. While clones from intermittent habitats showed somewhat stronger differential expression in response to acute hypoxia than those from permanent habitats, contrary to predictions, there were no significant hypoxia-by-habitat of origin or chronic-by-acute treatment interactions. GO enrichment analysis revealed a possible hypoxia tolerance role by accelerating the molting cycle and regulating neuron survival through up-regulation of cuticular proteins and neurotrophins, respectively.
2022-07-05 | GSE207385 | GEO
Project description:In this study, we employed Multiplex Bisulfite Sequencing (MBS) to measure CpG methylation within a ~500 bp region around the transcription start of six thermal/hypoxia biomarker genes (cirbp, jund, pdk3, prdx6, serpinh, ucp2) in the liver of post-smolt Atlantic salmon following short-term (3 days) and prolonged (4 weeks) exposure to i) high temperature (20°C) and normoxia (~100% air saturation) (Warm & Normoxic - WN); or ii) high temperature (20°C) and moderate hypoxia (~70% air saturation) (Warm & Hypoxic - WH) as compared to iii) control conditions (12°C, ~100% air saturation) (Control - CT).We found distinct CpG methylation profiles for each treatment group based on responsive CpG sites that were strongly dependent on the duration of the exposure (i.e., 3 days vs. 4 weeks at 20°C) and also differed between regulatory genomic regions (i.e., 5’upstream region, 5’UTR, first exon, and first intron). Several of these changes in CpG methylation were highly correlated with changes in gene expression, and can be considered as potential epigenetic marks (epimarkers).
2021-01-11 | GSE153343 | GEO
Project description:Expression data from mouse aorta with chronic intermittent hypoxia exposure
| PRJNA606452 | ENA
Project description:Background: Hypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ in their transcriptional response to hypoxia. Results: Here, we report that HIFs fail to bind CpG dinucleotides that are methylated in their consensus binding sequence, both in in vitro biochemical binding assays and in vivo studies of differentially methylated isogenic cell lines. Based on in silico structural modelling, we show that 5-methylcytosine indeed causes steric hindrance in the HIF binding pocket. A model wherein cell-type-specific methylation landscapes, as laid-down by the differential expression and binding of other transcription factors under normoxia control cell-type-specific hypoxia responses is observed. We also discover ectopic HIF binding sites in repeat regions which are normally methylated. Genetic and pharmacological DNA demethylation, but also cancer-associated DNA hypomethylation, expose these binding sites, inducing HIF-dependent expression of cryptic transcripts. In line with such cryptic transcripts being more prone to cause double-stranded RNA and viral mimicry, we observe low DNA methylation and high cryptic transcript expression in tumours with high immune checkpoint expression, but not in tumours with low immune checkpoint expression, where they would compromise tumour immunotolerance. In a low-immunogenic tumour model, DNA demethylation upregulates cryptic transcript expression in a HIF-dependent manner, causing immune activation and reducing tumour growth. Conclusions: Our data elucidate the mechanism underlying cell-type specific responses to hypoxia, and suggest DNA methylation and hypoxia to underlie tumour immunotolerance.
2020-06-18 | GSE85352 | GEO
Project description:Background: Hypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ in their transcriptional response to hypoxia. Results: Here, we report that HIFs fail to bind CpG dinucleotides that are methylated in their consensus binding sequence, both in in vitro biochemical binding assays and in vivo studies of differentially methylated isogenic cell lines. Based on in silico structural modelling, we show that 5-methylcytosine indeed causes steric hindrance in the HIF binding pocket. A model wherein cell-type-specific methylation landscapes, as laid-down by the differential expression and binding of other transcription factors under normoxia control cell-type-specific hypoxia responses is observed. We also discover ectopic HIF binding sites in repeat regions which are normally methylated. Genetic and pharmacological DNA demethylation, but also cancer-associated DNA hypomethylation, expose these binding sites, inducing HIF-dependent expression of cryptic transcripts. In line with such cryptic transcripts being more prone to cause double-stranded RNA and viral mimicry, we observe low DNA methylation and high cryptic transcript expression in tumours with high immune checkpoint expression, but not in tumours with low immune checkpoint expression, where they would compromise tumour immunotolerance. In a low-immunogenic tumour model, DNA demethylation upregulates cryptic transcript expression in a HIF-dependent manner, causing immune activation and reducing tumour growth. Conclusions: Our data elucidate the mechanism underlying cell-type specific responses to hypoxia, and suggest DNA methylation and hypoxia to underlie tumour immunotolerance.
2020-06-18 | GSE85351 | GEO
Project description:Antenatal hypoxia has critial impacts on fetal heart development. The molecular mechanism of the antenaltal hypoxia effect on the heart development is still unknown. We performed DNA methylome and transcriptome analyses of antenatal hypoxia induced rat fetal and adult offspring hearts to understand the hypoxia-mediated epigenomic programming in the heart development. Heart tissue from fetal (E21) and adult rat (5 months old) were collected. mRNA and genomic DNA methylation profiles of the heart tissue were generated by RNAseq and reduced representation bisulfite seuqencing (RRBS) techniques. We found 323 and 112 differential expressed genes between control and hypoxia groups in the fetal and adult hearts, respectively. Meanwhile, 2828 and 2193 differential methylated regions were identified in the fetal and adult hearts. Furthermore, opposite gobal DNA methylation pattern changes in transcription start site regions (TSS ± 1kb) were observed between fetal and adult hearts. Combining transcriptome, data indicates a significant difference in the responding genes and pathways between fetal and adult hearts in responding to the antenatal hypoxia. Our study provides an initial framework and new insights into fetal hypoxia-mediated epigenetic programming of pro-inflammatory phenotype in the heart development, linking antenatal stress, and developmental programming of heart vulnerability to disease later in life.
2019-04-25 | GSE129874 | GEO