Heme Deficient vs Wild Type in Low Iron
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE3470 | GEO | 2005/10/18
SECONDARY ACCESSION(S): PRJNA93417
REPOSITORIES: GEO
Similar Datasets
Project description:Heme Deficient or Wild Type (normal heme) for 6 hrs with iron chelation by BPS. Single Experiment with Probe Reversal 1. GSM78518 (Cy3) vs GSM78519 (Cy5) 2. GSM78520 (Cy3) vs GSM78521 (Cy5)
2010-06-30 | E-GEOD-3470 | biostudies-arrayexpress
Project description:Iron plays the central role in the oxygen transport by the erythrocyte as a constituent of heme and hemoglobin. The importance of iron and heme also resides in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is inactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1 mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1–/– mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin.
2016-12-14 | GSE78955 | GEO
Project description:Haemophilus influenzae frequently causes human disease, and humans are it’s sole niche. This bacterium has an absolute requirement for both a porphyrin and an iron source for aerobic growth, and exogenous heme can satisfy both requirements. Heme and iron can be acquired by H. influenzae from free or human protein-bound sources. The ability to selectively regulate the acquisition of heme and iron from physiological sources is a major virulence determinant for this microorganism. We utilized whole genome arrays to identify the full set of H. influenzae Rd KW20 iron and heme regulated genes. Condition specific RNA was derived from cells starved for both heme and iron and cells from the same culture 20 mins after the addition of exogenous iron and heme. The results identified 162 genes with a change in transcription ≥ 1.5 fold. Eighty genes in 42 operons were preferentially expressed under iron/ heme starvation; 82 genes in 50 operons were preferentially expressed under iron/heme replete conditions. In each case, all genes contained within the operon were co-regulated. The former group included genes encoding proteins known to have a role in iron and heme uptake as well as several hypothetical ORFs. Enzymes involved in the gluconeogenesis pathway and glycogen biosynthesis were also upregulated. The genes showing increased transcription immediately after the addition of iron and heme primarily encode proteins involved with aerobic respiration and protein biosynthesis, consistent with a relaxation of starvation. Genomic transcriptional profiling provides a more complete understanding of the effects of iron and heme availability. Keywords: Transcription analyses
2006-07-28 | GSE5061 | GEO
Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Global gene expression pattern of bone marrow-derived macrophages generated with GM-CSF in vitro and treated with heme were compared to those treated with vehicle at 6 hours, 24 hours, and 72 hours after treatment.
2014-03-14 | GSE46983 | GEO
Project description:Obesity is an independent risk factor for colorectal cancer (CRC) although the underlying mechanisms have not been elucidated. Dietary nutrients play a key role in both the prevention and promotion of CRC. While iron is an essential nutrient, excess iron is associated with carcinogenesis. Unlike the systemic compartment, the intestinal lumen lacks an efficient system to regulate iron. In conditions when dietary iron malabsorption and intestinal inflammation co-exist, greater luminal iron is associated with increased intestinal inflammation and a shift in the gut microbiota to more pro-inflammatory strains. However, treatments designed to reduce luminal, including diet restriction and chelation, are associated with lower intestinal inflammation and the colonization of protective gut microbes. Obesity is associated with inflammation-induced, hepcidin-mediated, iron metabolism dysfunction characterized by iron deficiency and dietary iron malabsorption. Obesity is also linked to intestinal inflammation. Currently, there is a fundamental gap in understanding how altered iron metabolism impacts CRC risk in obesity.
The investigator’s objective is to conduct a crossover controlled feeding trial of: 1) a "Typical American" diet with "high" heme/non-heme iron", 2) a "Typical American" diet with "low" iron, and 3) a Mediterranean diet with "high" non heme iron and examine effects on colonic and systemic inflammation and the gut microbiome.
| 2274754 | ecrin-mdr-crc
Project description:Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis. Global gene expression pattern of bone marrow-derived macrophages generated with GM-CSF in vitro and treated with heme were compared to those treated with vehicle at 6 hours, 24 hours, and 72 hours after treatment. GM-CSF cultures of Spic(igfp/igfp) BM cells were treated with heme (80 µm) or vehicle after 6 days in culture. Adherent fraction of cells were harvested 6 hours, 24 hours, and 72 hours after treatment and RNA was isolated using an RNeasy mini kit (Qiagen) and submitted for amplification, labeling and hybridization. Expression values were analyzed after RMA quantile normalization using ArrayStar software (DNASTAR).
2014-03-14 | E-GEOD-46983 | biostudies-arrayexpress
Project description:Macrophages are central in regulating iron homeostasis. Transcription repressor Bach1 regulates by heme. Here we investigated the relationship between heme-regulated Bach1 and bone marrow derived macrophage. We found that Bach1 KO macrophage showed that up-regulated genes were the process that iron-heme homeostasis and maintenance related gene compared with WT. Our results suggest that Bach1 expression is important to the heme homeostasis and maintenance in the bone marrow derived macrophage.
2019-03-30 | GSE79717 | GEO
Project description:Iron and heme play central roles in red blood cell production. However, the mechanisms by which iron and heme levels coordinate erythropoiesis remain incompletely understood. HRI is a heme-regulated kinase that controls translation by phosphorylating eIF2a. Here, we investigate the global impact of iron, heme and HRI on protein translation in vivo in murine primary erythroblasts using ribosome profiling. By defining the underlying changes in translation during iron and HRI deficiencies, we validate known regulators of this process, including Atf4, and identify novel pathways such as co-regulation of ribosomal protein mRNA translation. Surprisingly, we found that heme and HRI pathways, but not iron-regulated pathways, mediate the major protein translational and transcriptional responses to iron deficiency in erythroblasts in vivo and thereby identify previously unappreciated regulators of erythropoiesis. Our genome-wide study uncovers the major impact of the HRI-mediated integrated stress response for the adaptation to iron deficiency anemia.
2018-09-03 | GSE119365 | GEO
Project description:Porphyromonas gingivalis is a keystone pathogen responsible for oral microbiome dysbiosis, the development of periodontal disease, and may be involved in the development of systemic comorbidities. As a heme auxotroph, P. gingivalis relies on host hemoproteins as its primary sources of heme and iron. Although heme acquisition in P. gingivalis is relatively well characterized, considerably less is known about its pathways for iron uptake and the regulation of iron and heme homeostasis. P. gingivalis encodes four enzymes associated with the heme biosynthesis pathway, namely HemD, HemN, HemG, and HemH. HemH is a ferrochelatase responsible for the final step of heme biosynthesis, catalyzing the insertion of ferrous iron (Fe²⁺) into protoporphyrin IX. In addition, P. gingivalis expresses the Iht system, which plays a role in iron/heme utilization. One of its components, IhtB, is a heme-binding protein homologous to CbiK cobaltochelatases. Based on this homology, IhtB is hypothesized to function as a reverse ferrochelatase, facilitating the removal of iron from heme and thereby contributing to iron acquisition. This study aimed to investigate the effect of ihtB and hemH gene deletions on P. gingivalis gene expression under heme- and iron-replete conditions, to elucidate the roles of IhtB and HemH chelatases in heme and iron homeostasis.
2026-03-03 | E-MTAB-16135 | biostudies-arrayexpress
Project description:Iron deficiency is a highly prevalent nutrient deficiency and the most common cause of anemia. Although iron deficiency exacerbates cardiovascular disease, the direct impact of iron deficiency on the vasculature remains unstudied. Human lymphatic and arterial endothelial cells were treated with deferoxamine for 24 hours to assess the impact of iron deficiency on endothelial cell phenotypes. We found iron chelation upregulated the expression of arterial makers in both cell types. In lymphatic endothelial cells, iron chelation decreased the expression of lymphatic markers. These data suggest iron chelation shifts endothelial cells toward an arterial phenotype.
2025-12-31 | GSE314015 | GEO