Ascorbic acid reprogrames epigenome and epitranscriptome by recycling Fe (III) into Fe (II) in the catalytic cycle of dioxygenases
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ABSTRACT:
PROVIDER: PRJNA1014456 | ENA |
REPOSITORIES: ENA
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Project description:Ascorbic acid has been reported to stimulate DNA iterative oxidase TET enzymes, Jumonji C-domain-containinghistone demethylase and potentially RNA m6A demethylase FTO and ALKBH5 as a cofactor. Although ascorbic acid has been widely investigated in reprogramming DNA and histone methylation status in vitro, in cell lines and mouse models, its specific role in the catalytic cycle of dioxygenases remains enigmatic. Here we systematically investigated the stimulation of ascorbic towards TET2, ALKBH3, histone demethylases and FTO. We find that ascorbic acid reprograms epitranscrip-tome by erasing the hypermethylated m6A sites. Biochemistry and Electron spin resonance (ESR) assays demonstrate that ascorbic acid enters the active pocket of dioxygenases, reduces Fe (III), either incorporated upon protein synthesis or generated upon rebounding the hydroxyl radical during oxidation, into Fe (II). Finally, we propose a new model for the catalytic cycle of dioxygenases by adding in the essential dynamic cofactor, ascorbic acid. Ascorbic acid refreshes and regenerates inactive dioxygenase through recycling Fe (III) into Fe (II) in a dynamic “hit-and-run” manner.
2024-02-01 | GSE242758 | GEO
Project description:Ascorbic acid has been reported to stimulate DNA iterative oxidase TET enzymes, Jumonji C-domain-containinghistone demethylase and potentially RNA m6A demethylase FTO and ALKBH5 as a cofactor. Although ascorbic acid has been widely investigated in reprogramming DNA and histone methylation status in vitro, in cell lines and mouse models, its specific role in the catalytic cycle of dioxygenases remains enigmatic. Here we systematically investigated the stimulation of ascorbic towards TET2, ALKBH3, histone demethylases and FTO. We find that ascorbic acid reprograms epitranscrip-tome by erasing the hypermethylated m6A sites. Biochemistry and Electron spin resonance (ESR) assays demonstrate that ascorbic acid enters the active pocket of dioxygenases, reduces Fe (III), either incorporated upon protein synthesis or generated upon rebounding the hydroxyl radical during oxidation, into Fe (II). Finally, we propose a new model for the catalytic cycle of dioxygenases by adding in the essential dynamic cofactor, ascorbic acid. Ascorbic acid refreshes and regenerates inactive dioxygenase through recycling Fe (III) into Fe (II) in a dynamic “hit-and-run” manner.
2024-02-01 | GSE242759 | GEO
Project description:Ascorbic acid reprogrames epigenome and epitranscriptome by recycling Fe (III) into Fe (II) in the catalytic cycle of dioxygenases (m6A)
| PRJNA1014463 | ENA
Project description:Ascorbic acid reprogrames epigenome and epitranscriptome by recycling Fe (III) into Fe (II) in the catalytic cycle of dioxygenases (RNA-Seq)
| PRJNA1014464 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-02-01 | GSE242760 | GEO
Project description:In addition to the role of antioxidant, ascorbic acid (reducing Vitamin C) is an important cofactor for Fe2+ and α-ketoglutarate (α-KG) dependent dioxygenases (Fe2+/α-KGDDs) that comprise many diverse enzymes, including collagen prolyl hydroxylases, jmjC (Jumonji C) domain containing histone demethylases, Ten-eleven translocation (TET) 5-methyl cytosine (5mC) dioxygenases, and N6-methyl adenosine (m6A) demethylase FTO and ALKBH5. Ascorbic acid was reported to induce global epigenetic reprogramming. Here we optimized the library construction flow chart of single-stranded DNA profiling method KAS-seq and utilized KAS-seq to profile transient chromatin states changes upon ascorbic acid treatment for 10 min. We identified several critical pathways affected by ascorbic acid treatment, providing some clues for explaining the reported positive impact of anti-cancer, anti-depression, and anti-obesity for taking ascorbic acid.
2023-07-25 | GSE237843 | GEO
Project description:Loss-of-function TET2 mutations (TET2MT) are common in myeloid neoplasia. TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. TET2MT thus result in hypermethylation and transcriptional repression. Ascorbic acid (AA) increases dioxygenase activity by facilitating Fe(III)/Fe(II) redox reaction and may alleviate some biological consequences of TET2MT by restoring dioxygenase activity. Here, we report the utility of AA in the prevention of TET2MT MN, clarify the mechanistic underpinning of the TET2-AA interactions, and demonstrate that the ability of AA to restore TET2 activity in cells depends on N- and C-terminal lysine acetylation and nature of TET2MT. Consequently, pharmacologic modulation of acetyltransferases and histone deacetylases may regulate TET dioxygenase-dependent AA effects. Thus, our study highlights the contribution of factors that may enhance or attenuate AA effects on TET2 and provides a rationale for novel therapeutic approaches including combinations of AA with class I/II HDAC inhibitor or sirtuin activators in TET2MT leukemia.
2020-09-09 | PXD020550 | Pride
Project description:We used RNA-Seq to compare the transcriptomes of Fe-replete vs. Fe-deficient vs. Fe-limited Chlamydomonas wild-type cells. Our RNA-Seq data revealed 90 and 49 genes to be specifically expressed under hetero-phototrophic and phototrophic conditions, respectively. Around 30 genes represent putative Fe-deficiency targets, independent of the carbon source used. Many of these Fe-specific responses are conserved between Chlamydomonas and land plants. We identified several transporters (NRAMP4, a CCC1-like proteins and a ferroportin homologue) all of them most likely being involved in intracellular Fe redistribution. RNA-seq of Chlamydomonas Fe-deficient and limited cells indicated that about 40% of differentially expressed genes represent proteins of unknown functions. Whereas Fe-deficiency gave us insides into putative Fe-specific responses, Fe-limitation revealed responses related to increased oxidative stress. Quantitative proteomics on the soluble Chlamydomonas extracts indicated a fair correlation between changes we detected at mRNA levels compared to changes in protein levels in Fe-deficient and Fe-limited Chlamydomonas. We found that Fe-deficient and Fe-limited cells have increased ascorbate levels, a major antioxidant molecule in plants. Ascorbate levels appear to be elevated by de novo synthesis via the L-Galactose pathway and recycling by monodehydroascorbate reductase. Fe-limited cells showed increased transcript and protein levels of enzymatic antioxidant components of the ascorbate-glutathione scavenging system (MSD3, MDAR1 or GSH1). Fe-limited cells showed the increase of several proteases indicative of elevated proteolitic activity under these severe nutrient limitation conditions.
2012-06-18 | GSE35305 | GEO
Project description:We reported the flg22-triggered immune responses in roots affect the iron deficiency responses and may link to the function of FLS2 and IMA1 in the root. To identify the underlying mechanism of how the root transcriptome profiles respond to +Fe, +Fe+flg22, -Fe, -Fe+flg22 respectively, and if the flg22 responses is dependent on the function of FLS2 and IMA1 in the root, we performed an mRNA-seq experiments in Col-0, fls2 and UBQ10::mCitrine-IMA1 with different treatments. The differentially expressed genes in response to +Fe, +Fe+flg22, -Fe, -Fe+flg22 were analyzed. It has 36 samples in total, with 3 biogical replicates for each condition and each genotype.
2023-10-09 | GSE213557 | GEO
Project description:We used RNA-Seq to compare the transcriptomes of Fe-replete vs. Fe-deficient vs. Fe-limited Chlamydomonas wild-type cells. Our RNA-Seq data revealed 90 and 49 genes to be specifically expressed under hetero-phototrophic and phototrophic conditions, respectively. Around 30 genes represent putative Fe-deficiency targets, independent of the carbon source used. Many of these Fe-specific responses are conserved between Chlamydomonas and land plants. We identified several transporters (NRAMP4, a CCC1-like proteins and a ferroportin homologue) all of them most likely being involved in intracellular Fe redistribution. RNA-seq of Chlamydomonas Fe-deficient and limited cells indicated that about 40% of differentially expressed genes represent proteins of unknown functions. Whereas Fe-deficiency gave us insides into putative Fe-specific responses, Fe-limitation revealed responses related to increased oxidative stress. Quantitative proteomics on the soluble Chlamydomonas extracts indicated a fair correlation between changes we detected at mRNA levels compared to changes in protein levels in Fe-deficient and Fe-limited Chlamydomonas. We found that Fe-deficient and Fe-limited cells have increased ascorbate levels, a major antioxidant molecule in plants. Ascorbate levels appear to be elevated by de novo synthesis via the L-Galactose pathway and recycling by monodehydroascorbate reductase. Fe-limited cells showed increased transcript and protein levels of enzymatic antioxidant components of the ascorbate-glutathione scavenging system (MSD3, MDAR1 or GSH1). Fe-limited cells showed the increase of several proteases indicative of elevated proteolitic activity under these severe nutrient limitation conditions. Sampling of Chlamydomonas CC-1021 (2137) cells cultivated photoheterotrophically (TAP) or phototrophically (minimal) under Fe-replete (20mM), Fe-deficient (1 mM) and Fe-limited (0.25 mM) conditions.
2012-06-18 | E-GEOD-35305 | biostudies-arrayexpress