Enterocyte-specific deletion of metal transporter Zip14 (Slc39a14) alters intestinal homeostasis through epigenetic mechanisms
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE210160 | GEO | 2022/12/14
REPOSITORIES: GEO
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Project description:Zinc has anti-inflammatory properties using mechanisms that are unclear. Zip14 (Slc39a14) is a zinc transporter induced by proinflammatory stimuli and is highly expressed at the basolateral membrane of intestinal epithelial cells (IECs). Enterocyte-specific Zip14 ablation (Zip14ΔIEC) in mice was developed to study the functions of this transporter in enterocytes. This gene deletion led to increased intestinal permeability, increased IL-6 and IFNγ expression, mild endotoxemia, and intestinal dysbiosis. RNA sequencing was used for transcriptome profiling. These analyses revealed differential expression of specific intestinal proinflammatory and tight junction (TJ) genes. Binding of transcription factors, including NF-κβ, STAT3, and CDX2, to appropriate promoter sites of these genes supports the differential expression shown with chromatin immunoprecipitation assays. Total histone deacetylase (HDAC), and specifically HDAC3, activities were markedly reduced with Zip14 ablation. Intestinal organoids derived from ΔIEC mice display TJ and cytokine gene dysregulation compared with control mice. Differential expression of specific genes was reversed with zinc supplementation of the organoids. We conclude that zinc-dependent HDAC enzymes acquire zinc ions via Zip14-mediated transport and that intestinal integrity is controlled in part through epigenetic modifications.NEW & NOTEWORTHY We show that enterocyte-specific ablation of zinc transporter Zip14 (Slc39a14) results in selective dysbiosis and differential expression of tight junction proteins, claudin 1 and 2, and specific cytokines associated with intestinal inflammation. HDAC activity and zinc uptake are reduced with Zip14 ablation. Using intestinal organoids, the expression defects of claudin 1 and 2 are resolved through zinc supplementation. These novel results suggest that zinc, an essential micronutrient, influences gene expression through epigenetic mechanisms.
| S-EPMC9925170 | biostudies-literature
Project description:Enterocyte-specific deletion of metal transporter Zip14 (Slc39a14) alters intestinal homeostasis through epigenetic mechanisms
| PRJNA864065 | ENA
Project description:Zinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to determine how zinc is important to placental morphogenesis. Global placental gene expression at gestational day 18.5 was analysed using microarray to determine the effects of zinc deficiency on placental function.
2018-02-13 | GSE97112 | GEO
Project description:Plants are exposed to antibiotics produced by soil microorganisms but little is known about their responses at the transcriptional level. Likewise, few endogenous mechanisms of antibiotic resistance have been reported. The Arabidopsis thaliana ATP Binding Cassette (ABC) transporter AtWBC19 (ABCG19) is known to confer kanamycin resistance, but the exact mechanism of resistance is not well understood. Here we examined the transcriptomes of control seedlings and wbc19 mutant seedlings using RNA-seq analysis. Exposure to kanamycin indicated changes in the organization of the photosynthetic apparatus, metabolic fluxes and metal uptake. Elemental analysis showed a 60% and 80% reduction of iron uptake in control and wbc19 mutant seedlings respectively, upon exposure to kanamycin. The drop in iron content was accompanied by the upregulation of the gene encoding for FERRIC REDUCTION OXIDASE 6 (FRO6) in mutant seedlings but not by the differential expression of other transport genes known to be induced by iron deficiency. In addition, wbc19 mutants displayed a distinct expression profile in the absence of kanamycin. Most notably, the expression of several zinc ion binding proteins, including ZINC TRANSPORTER 1 PRECURSOR (ZIP1), was increased, suggesting abnormal zinc uptake. Elemental analysis confirmed a 50% decrease of zinc content in wbc19 mutants. Thus, the antibiotic resistance gene WBC19 appears to also have a role in zinc uptake. Examination of transcriptome in control and wbc19 mutant seedlings with or without exposure to kanamycin.
2014-06-20 | E-GEOD-58662 | biostudies-arrayexpress
Project description:Plants are exposed to antibiotics produced by soil microorganisms but little is known about their responses at the transcriptional level. Likewise, few endogenous mechanisms of antibiotic resistance have been reported. The Arabidopsis thaliana ATP Binding Cassette (ABC) transporter AtWBC19 (ABCG19) is known to confer kanamycin resistance, but the exact mechanism of resistance is not well understood. Here we examined the transcriptomes of control seedlings and wbc19 mutant seedlings using RNA-seq analysis. Exposure to kanamycin indicated changes in the organization of the photosynthetic apparatus, metabolic fluxes and metal uptake. Elemental analysis showed a 60% and 80% reduction of iron uptake in control and wbc19 mutant seedlings respectively, upon exposure to kanamycin. The drop in iron content was accompanied by the upregulation of the gene encoding for FERRIC REDUCTION OXIDASE 6 (FRO6) in mutant seedlings but not by the differential expression of other transport genes known to be induced by iron deficiency. In addition, wbc19 mutants displayed a distinct expression profile in the absence of kanamycin. Most notably, the expression of several zinc ion binding proteins, including ZINC TRANSPORTER 1 PRECURSOR (ZIP1), was increased, suggesting abnormal zinc uptake. Elemental analysis confirmed a 50% decrease of zinc content in wbc19 mutants. Thus, the antibiotic resistance gene WBC19 appears to also have a role in zinc uptake.
2014-06-20 | GSE58662 | GEO
Project description:Zinc deficiency is detrimental to organisms highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within zebrafish gill. This tissue represents a model system for studying ion absorption across polarised cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals. Zebrafish were treated with either zinc-depleted (water = 2.61 μg L-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 μg L-1; diet = 233 mg kg-1) conditions for two weeks. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array. Global transcript levels were measured in zebrafish gills using a oligonucleotide array either zinc-depleted or zinc-adequate diet. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array
2010-05-20 | E-GEOD-21894 | biostudies-arrayexpress
Project description:Deficiency of the micronutrient zinc is a widespread condition in agricultural soils, generating a negative impact on crop quality and yield. Nevertheless, there is insufficient knowledge on the regulatory and molecular mechanisms underlying the plant response to inadequate zinc nutrition. Hydroponically-grown Arabidopsis thaliana plants (WT Col-0 and the T-DNA insertion double mutant bzip19 bzip23) were subjected to zinc deficiency, sufficiency and excess. The particular role of the bZIP19 and bZIP23 transcription factors was investigated via the bzip19 bzip23 double mutant.
2016-01-28 | GSE77286 | GEO
Project description:Zinc deficiency is detrimental to organisms highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within zebrafish gill. This tissue represents a model system for studying ion absorption across polarised cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals. Zebrafish were treated with either zinc-depleted (water = 2.61 μg L-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 μg L-1; diet = 233 mg kg-1) conditions for two weeks. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array.
2010-05-20 | GSE21894 | GEO
Project description:Heavy metals are essential integral parts of cells and environmental toxicants, whose deregulation is associated with severe cellular dysfunction and various diseases. The Hippo pathway plays a critical role in organ size control and cancer development. In this study, we use RNA-Seq to investigate the role of the Hippo pathway in regulating heavy metal response gene transcription. Specifically, the difference of transcriptional profiles between the wild-type and the Hippo pathway kinases LATS1/2-deficient HEK293A cells was examined under control- and heavy metals zinc and cadimuim treated-conditions.
2021-10-02 | GSE163156 | GEO
Project description:How cells safeguard essential zinc-dependent functions during zinc deficiency is poorly understood. A long-debated strategy is whether soluble metal-trafficking chaperones exist to prioritize specific zinc-dependent proteins. We identified a eukaryotic family of metallochaperones that physically interacts with zinc-dependent methionine aminopeptidase type I (MAP1) in human and yeast. Deletion of the yeast metallochaperone-encoding gene NMC1 (formerly YNR029c) leads to a zinc-deficiency growth defect and defective initiator methionine cleavage caused by loss of Map1p activity. To better understand the observed fitness defects due to the lack of NMC1 under zinc deficiency, we used proteomics with Tandem Mass Tag (TMT) quantitation derived from WT, nmc1Delta, and map2Delta nmc1Delta strains grown in zinc-limited (1 uM) or zinc-replete (100 uM) conditions. Proteomics reveal global impacts due to the loss of NMC1 and Map1p function, including mis-regulation of the Zap1p regulon, and suggests that Nmc1p is required to avoid a compounding effect of Map1p dysfunction on cell survival during zinc deficiency.
| MSV000088135 | MassIVE