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Whole genome bisulfite sequencing analysis to examine the effect of the iron chelator deferoxamine on DNA methylation levels in 3T3-L1 pre-adipocyte cells

ABSTRACT: Adipocyte differentiation has been shown to require iron, but the underlying mechanism remains elusive. Ferrous iron ion is known to function as a co-factor for alpha-ketoglutarate-dependent dioxygenases, including demethylases for histones, DNA, and RNA. Previously we reported several alpha-ketoglutarate-dependent histone demethylases as critical epigenetic regulators during adipogenesis. These lines of evidence led us to hypothesize that iron orchestrates epigenetic/epitranscriptional regulations during adipogenesis by controlling demethylation activities. In this study, we conducted genome-wide analysis on methylation landscapes of histones, DNA, and RNA in differentiation of 3T3-L1 pre-adipocytes. Using the iron chelator deferoxamine, we demonstrate here how dynamically methylation levels of histones, DNA, and RNA are regulated by iron during adipogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE174134 | GEO | 2023/04/23

REPOSITORIES: GEO

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ChIP-seq analysis to examine the effect of the iron chelator deferoxamine on histone methylation levels in 3T3-L1 pre-adipocyte cells

Project description:Adipocyte differentiation has been shown to require iron, but the underlying mechanism remains elusive. Ferrous iron ion is known to function as a co-factor for alpha-ketoglutarate-dependent dioxygenases, including demethylases for histones, DNA, and RNA. Previously we reported several alpha-ketoglutarate-dependent histone demethylases as critical epigenetic regulators during adipogenesis. These lines of evidence led us to hypothesize that iron orchestrates epigenetic/epitranscriptional regulations during adipogenesis by controlling demethylation activities. In this study, we conducted genome-wide analysis on methylation landscapes of histones, DNA, and RNA in differentiation of 3T3-L1 pre-adipocytes. Using the iron chelator deferoxamine, we demonstrate here how dynamically methylation levels of histones, DNA, and RNA are regulated by iron during adipogenesis.

2023-04-23 | GSE174133 | GEO

RNA-seq analysis to examine the effect of the iron chelator deferoxamine on gene expression profile in 3T3-L1 pre-adipocyte cells

2023-04-23 | GSE174132 | GEO

Treatment of a human lymphoblastoid cell line with the iron chelator deferoxamine

Project description:We treated lymphoblast cells with the iron chelator deferoxamine (DFO) for 60 hours to determine if iron chelation would affect the levels of intron lariats.

2022-03-23 | GSE199077 | GEO

Transcriptomics analysis of iron chelator deferoxamine treated human tumor colonoids.

Project description:To investigate the detailed molecular mechanisms for the regulatory role of iron in colorectal cancer, RNA-seq analysis was performed on RNA isolated from untreated control and deferoxamine treated human tumor colonoids.

2023-08-01 | GSE185738 | GEO

Treatment of a human lymphoblastoid cell line with the iron chelator deferoxamine

Project description:Treatment of a human lymphoblastoid cell line with the iron chelator deferoxamine

| PRJNA818298 | ENA

Analysis of deferoxamine treated leaves and roots: Arabidopsis transcriptome in response to deferoxamine

Project description:au08-04_dfo - analysis of deferoxamine treated leaves and roots - What are the effects of the siderophore deferoxamine on Arabidopsis leaves and roots? - Plants were allowed to grow for 5-6 weeks. The nutrient solution contains 0.25 mM Ca(NO3)2.4H2O, 1mM KH2PO4, 0.5 mM KNO3, 1mM MgSO4.7H2O, 50 µM H3BO3, 19 µM MnCl2.4H2O, 10 µM ZnCl2, 1 µM CuSO4.5H2O, 0.02 µM Na2MoO4.2H2O and 50 µM FeNa-EDTA. Plants were subjected to an 8 h light/16 h dark cycle, at 19°C, with 70% relative humidity. Leaves of six week old hydroponically grown A. thaliana Col0 plants were infiltrated with 1mM deferoxamine or sterile distilled water. Leaves were harvested 7 and 24 h.p.i. Keywords: time course,treated vs untreated comparison

2010-06-01 | GSE18976 | GEO

Sorted tumor RNA-seq of syngeneic murine mutant IDH1 ICC tumor model treated with IDH1 inhibitor against vehicle

Project description:IDH1 is the most commonly mutated metabolic gene across human cancers, with the highest mutational frequency observed in AML, glioma, chondrosarcoma, and intrahepatic cholangiocarcinoma. Mutations of the hot spot R132 codon alter the activity of the IDH1 enzyme, resulting in the NADPH-dependent conversion of alpha-ketoglutarate to (R)-2-hydroxyglutarate [(R)-2HG], which accumulates to mM levels within tumors. (R)-2HG competitively inhibits a range of enzymes that utilize alpha-ketoglutarate. Targets include the JmjC family histone demethylases and TET family DNA demethylases whose inhibition is linked to the altered epigenetic state characteristic of many mIDH tumors. To gain insight into the mechanisms underlying the anti-tumor efficacy of inhibition of mutant IDH1 we conducted RNA-sequencing (RNA-seq) analysis of purified tumor cells. For these studies, the immune-competent 2205 subcutaneous allograft model was treated with AG120 or vehicle for 6 days and non-tumor cells were removed by magnetic bead sorting (negative selection for CD45+ immune cells, CD31+ endothelial cells, TER119+ erythrocytes, and CD90.2+ fibroblasts).

2021-11-23 | E-MTAB-11112 | biostudies-arrayexpress

Effect of deferasirox and deferoxamine treatment on hematopoietic stem cells gene expression

Project description:To investigate new molecular pathways affected by deferasirox or deferoxamine able to explain hematopoiesis restoration

2019-09-02 | E-MTAB-6658 | biostudies-arrayexpress

Histone arginine demethylation by RDMe1

Project description:Histone methylation mainly occurs on lysine and arginine residues. While lysine methylation can be removed by LSD1 and JmjC domain-containing demethylases, the existence of histone arginine demethylases is highly controversial. Here, we performed a high-content cell-based screening of a cDNA library containing 2,500 nuclear proteins and identified RDMe1 as a histone arginine demethylase. Overexpression of RDMe1 in HEK293T cells reduces H3R2me1/2a and H4R3me1/2a levels. In vitro, RDMe1 specifically demethylates H3R2me1/2a and H4R3me1/2a, and generates formaldehyde and succinate. The enzymatic activity requires Fe(II) and α-ketoglutarate as cofactors. RDMe1 is mainly located in the nucleolar and regulates rRNA transcription by demethylating H3R2me2a. ChIP-seq reveals that RDMe1 demethylates H4R3me2a in the promoter in a genome-wide scale. NMR reveals that RDMe1 binds iron and substrate peptides with N and C termini, respectively. Mutation of the iron binding residues abolished the binding and the demethylase activity. Thus, we identify a histone arginine demethylase and reveal the reversibility of arginine methylation.

2022-01-09 | GSE124890 | GEO

Iron excess limits HHIPL2 gene expression and decreases osteoblastic activity in human MG-63 cells

Project description:Our transcriptomic data shows that iron impact on human osteoblastic MG-63 cells by decreasing HHIPL-2 gene expression (2 fold ratio). This impact is corrected in presence of deferoxamine. Additional biological experiments in the manuscript suggest that the iron related modulation of HHIPL-2 gene expression could take place in the decrease of osteoblastic markers in the MG-63 cell line. Such mechanisms could participate to the development of osteoporosis in iron overloaded patients. One-condition experiment, iron exposure using ferric ammonium citrate (FAC) at two concentrations (5 and 20M-BM-5M) was compared to basal condition. Additional conditions include: deferoxamine (DFO) (iron chelator) 20M-BM-5M alone or in addition to FAC 20M-BM-5M. For each condition five biological replicates were performed (independent experiments).

2012-09-01 | E-GEOD-30774 | biostudies-arrayexpress

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