Histone acetylases are required for iron homeostasis
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ABSTRACT:
PROVIDER: PRJEB77025 | ENA |
REPOSITORIES: ENA
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Project description:The Endoplasmic Reticulum–Mitochondria Encounter Structure (ERMES) is a protein complex that tethers the two organelles and creates the physical basis for communication between them. ERMES functions in lipid and calcium exchange between the ER and mitochondria, mitochondrial protein import and maintenance of mitochondrial morphology and genome. Here we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of ERMES known roles in calcium regulation, phospholipid biosynthesis or mitochondrial biology. A mutation in the vacuolar protein sorting 13 (VPS13) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our study reveals that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels.
2017-06-20 | GSE99499 | GEO
Project description:Beside suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron, a fundamental element for all living cells, is required for Treg expansion, is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated proliferating Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by a severe impairment in perinatal Treg expansion. CD71-null Tregs display decreased proliferation and mitochondrial functions, and a tissue-Treg signature loss. In the perinatal life, CD71 deficiency in Tregs triggered a hepatic response to iron overload, characterized by increased hepcidin transcription and iron accumulation in macrophages. A lower bacterial diversity, and a reduction of beneficial species, were detected in the faecal microbiota of CD71 conditional knock-out neonates. Our findings indicate that the CD71-mediated iron absorption is required for Treg perinatal expansion and controls the systemic iron homeostasis, which in turn shapes the bacterial gut colonization.
2024-07-02 | GSE212688 | GEO
Project description:The study of gene expression profile of iron homeostasis-related genes using Affymetrix GeneChips in conjunction with the pathological assessment of hepatic iron content in hepatocellular carcinoma (HCC) samples offers a new strategy to understand the role of hepatic iron overload in hepatocarcinogenesis.
2007-01-10 | E-MEXP-84 | biostudies-arrayexpress
Project description:Disruption of local iron homeostasis is a common feature of neurodegenerative diseases. We focused on dopaminergic neurons, asking how iron transport proteins modulate iron homeostasis in vivo. Inactivation of the transmembrane iron exporter ferroportin had no apparent consequences. However, loss of the transferrin receptor 1, involved in iron uptake, caused profound, age-progressive neurodegeneration with features similar to Parkinson’s disease. There was gradual loss of dopaminergic projections in the striatum with subsequent death of dopaminergic neurons in the substantia nigra. After depletion of 30% of the neurons the mice developed neurobehavioral parkinsonism, with evidence of mitochondrial dysfunction and impaired mitochondrial autophagy. Molecular analysis revealed strong signatures indicative of attempted axonal regeneration, a metabolic switch to glycolysis and the unfolded protein response. We speculate that cellular iron deficiency may contribute to neurodegeneration in human patients Using Ribotag technology, from mouse ventral midbrain lysates, we isolated actively translated mRNA species from control and Transferrin receptor 1-null dopaminergic neurons. Two mouse ages were used 3 wks (early neurodegeration) 10 wks (late neurodegeneration)
2015-03-11 | E-GEOD-66730 | biostudies-arrayexpress
Project description:Because iron toxicity and deficiency are equally life threatening, maintaining intracellular iron levels within a narrow optimal range is critical for nearly all known organisms. However, regulatory mechanisms that establish homeostasis are not well understood in organisms that dwell in environments at the extremes of pH, temperature, and salinity. Under conditions of limited iron, the extremophile Halobacterium salinarum, a salt-loving archaeon, mounts a specific response to scavenge iron for growth. We have identified and characterized the role of two transcription factors (TFs), Idr1 and Idr2, in regulating this important response. An integrated systems analysis of TF knockout gene expression profiles and genome-wide binding locations in the presence and absence of iron has revealed that these TFs operate collaboratively to maintain iron homeostasis. In the presence of iron, Idr1 and Idr2 bind near each other at 24 loci in the genome, where they are both required to repress some genes. In contrast, Idr1 and Idr2 are both necessary to activate other genes in a putative a feed forward loop. Even at loci bound independently, the two TFs target different genes with similar functions in iron homeostasis. We discuss conserved and unique features of the Idr1-Idr2 system in the context of similar systems in organisms from other domains of life. Data in this GEO archive are linked to the publication: Schmid AK, Pan M, Sharma K, Baliga NS.2011. Two transcription factors are necessary for iron homeostasis in a salt-dwelling archaeon.Nucleic Acids Res.39(7):2519-33.
2011-06-03 | GSE29705 | GEO
Project description:All living cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here, we report a universal eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of genes encoding high-affinity leucine transporters and RAPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency (ID) supersedes other nutrient inputs into mTORC1. This process occurs in vivo, and is not an indirect effect by canonical iron-utilizing pathways. Elevated expression of KDM3B targets is associated with reduced survival in a subset of human cancers and ID represses mTORC1 in patient-derived tumor cells and sensitizes cancer cells to chemotherapy. These data demonstrate a novel mechanism of eukaryotic iron sensing through dynamic chromatin remodeling and repression of mTORC1 mediated anabolism. Due to ancestral eukaryotes sharing homologues of KDMs and mTORC1 core components, this pathway likely predated the emergence of the other kingdom-specific nutrient sensors for mTORC1
2023-07-18 | GSE214019 | GEO
Project description:Because iron toxicity and deficiency are equally life threatening, maintaining intracellular iron levels within a narrow optimal range is critical for nearly all known organisms. However, regulatory mechanisms that establish homeostasis are not well understood in organisms that dwell in environments at the extremes of pH, temperature, and salinity. Under conditions of limited iron, the extremophile Halobacterium salinarum, a salt-loving archaeon, mounts a specific response to scavenge iron for growth. We have identified and characterized the role of two transcription factors (TFs), Idr1 and Idr2, in regulating this important response. An integrated systems analysis of TF knockout gene expression profiles and genome-wide binding locations in the presence and absence of iron has revealed that these TFs operate collaboratively to maintain iron homeostasis. In the presence of iron, Idr1 and Idr2 bind near each other at 24 loci in the genome, where they are both required to repress some genes. In contrast, Idr1 and Idr2 are both necessary to activate other genes in a putative a feed forward loop. Even at loci bound independently, the two TFs target different genes with similar functions in iron homeostasis. We discuss conserved and unique features of the Idr1-Idr2 system in the context of similar systems in organisms from other domains of life. Data in this GEO archive are linked to the publication: Schmid AK, Pan M, Sharma K, Baliga NS.2011. Two transcription factors are necessary for iron homeostasis in a salt-dwelling archaeon.Nucleic Acids Res.39(7):2519-33. The Δura3 parent, Δidr2 and Δidr1, and Δ idr1Δidr2 mutant strains were grown to mid-logarithmic phase (OD600 ~0.4 – 0.8) in CDM with all trace metals except iron. Cultures were split in half and FeSO4 was added to one half, while the other was continued under iron limitation. 8-mL samples were collected from each culture every 20 minutes for 60 minutes (see also experimental design, Supplementary Figure 1, Schmid et al., 2011). RNA from two biological replicate time courses were prepared, averages of these replicates are reported in the published study, whereas data from each replicate are reported here. The zero time point was harvested immediately before the addition of iron. Each Sample is based on two arrrays (one with dye-swap).
2011-06-03 | E-GEOD-29704 | biostudies-arrayexpress
Project description:Disruption of local iron homeostasis is a common feature of neurodegenerative diseases. We focused on dopaminergic neurons, asking how iron transport proteins modulate iron homeostasis in vivo. Inactivation of the transmembrane iron exporter ferroportin had no apparent consequences. However, loss of the transferrin receptor 1, involved in iron uptake, caused profound, age-progressive neurodegeneration with features similar to Parkinson’s disease. There was gradual loss of dopaminergic projections in the striatum with subsequent death of dopaminergic neurons in the substantia nigra. After depletion of 30% of the neurons the mice developed neurobehavioral parkinsonism, with evidence of mitochondrial dysfunction and impaired mitochondrial autophagy. Molecular analysis revealed strong signatures indicative of attempted axonal regeneration, a metabolic switch to glycolysis and the unfolded protein response. We speculate that cellular iron deficiency may contribute to neurodegeneration in human patients
2015-03-11 | GSE66730 | GEO
Project description:Strict iron regulation is essential for normal brain function. The iron homeostasis, determined by the milieu of available iron compounds, is impaired in aging, neurodegenerative diseases and cancer. However, non-invasive assessment of different molecular iron environments implicating brain tissue's iron homeostasis remains a challenge. We present a novel magnetic resonance imaging (MRI) technology sensitive to the iron homeostasis of the living brain (the r1-r2*relaxivity). In vitro, our MRI approach reveals the distinct paramagnetic properties of ferritin, transferrin and ferrous iron. In the in vivo human brain, we validate our approach against ex vivo iron compounds quantification and gene expression. Our approach varies with the iron mobilization capacity across brain regions and in aging. It reveals brain tumors’ iron homeostasis, and enhances the distinction between tumor tissue and non- pathological tissue without contrast agents. Therefore, our approach may allow for non-invasive research and diagnosis of iron homeostasis in living human brains.
2023-08-11 | GSE240204 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE29704: Two transcription factors are necessary for iron homeostasis in a salt-dwelling archaeon [gene expression data] GSE29705: Two transcription factors are necessary for iron homeostasis in a salt-dwelling archaeon [ChIP-chip data] Refer to individual Series
2011-06-02 | E-GEOD-29706 | biostudies-arrayexpress