Gene expression analysis of the effect of Irx3 knockout in mouse hypothalamus compared with wild-type (in high-fat diet)
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Mus musculus
SUBMITTER: Noboru Sakabe
PROVIDER: E-MTAB-10186 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We performed 4C to analyze long-range interactions between the promoters of Rpgrip1l/Fto, Irx3, Irx5 and Irx6 and a region in the first intron of the FTO gene that has been associated with obesity. 3 whole mouse hypothalami were used to obtain the data.
2021-03-20 | E-MTAB-10195 | biostudies-arrayexpress
Project description:IRX3 is a transcriptional factor, which play important functions in developmental processes. But the role of IRX3 in immune cells are less studied. So we sequenced mRNA from BMDMs overexpressing GFP, IRX3, as well as two phosphorylation site mutants-S361A and S389A respectively, to address the roles of IRX3 in macrophages.
2021-07-29 | GSE178574 | GEO
Project description:Analysis of the roles of Irx3 and Irx5 transcription factors in mouse heart development and postnatal heart function. Results show that show that Irx3 and Irx5 have redundant function in the in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation. A postnatal deletion of Irx3 and Irx5 surprisingly results in a restoration of the repolarization gradient that is altered in Irx5 mutant hearts, suggesting a model whereby postnatal Irx3 activity is normally repressed by Irx5. 4 genotypes were analyzed: Irx5+/- (3 samples), Irx3-/-;Irx5+/- (4 samples), Irx5-/- (3 samples), Irx5-/-;Irx3-/- (4 samples). The Irx5+/- samples are the reference.
2012-06-19 | E-GEOD-38826 | biostudies-arrayexpress
Project description:Background IRX3 is implicated in genetic predisposition to obesity via the FTO variant locus. IRX3 shows FTO risk allele-dependent upregulation specifically during early adipogenesis, leading to a shift from energy dissipation to fat storage in mature adipocytes. However, how changes in IRX3 expression at one developmental stage affect cellular phenotype at a later stage remains unclear. We here hypothesize that IRX3 regulates adipocyte development via transcriptional modulation of epigenetic reprogramming factors. Methods We combined ChIP-, ATAC- and RNA-sequencing to map direct Irx3 target genes in regions of open chromatin during early adipogenesis of wild-type and Irx3-KO preadipocytes. Gene ontology analyses was performed to identify significantly enriched biological pathways. Denaturing western blotting was used to assess sumoylation levels, and the inhibitor ML-792 was used to specifically block sumoylation. Luciferase assays were performed to estimate effects of ML-792 on Pparγ activity. Bodipy lipid staining, immunofluorescence and qPCR were employed to assess adipogenic differentiation in 3D culture. Alkaline phosphatase and Alizarine Red S staining, as well as immunofluorescence and qPCR were used to assess osteogenic differentiation in 3D culture. Results We identified more than 300 Irx3 binding sites in preadipocytes, and these were almost exclusively restricted to promoter regions, with a strong enrichment of genes related to sumoylation, histone modifications and chromatin remodeling. Genes from every step of the sumoylation cycle were bound by Irx3 and differentially expressed in response to Irx3-KO, leading to increased global sumoylation levels in the KO cells. Irx3 ablation and elevated sumoylation inhibited Pparγ activity and adipogenic differentiation in preadipocytes, both of which could be restored by pharmacological inhibition of sumoylation. The Irx3-KO cells demonstrated reduced epigenetic suppression against osteogenesis, resulting in increased osteogenesis in 3D culture. Finally, osteogenesis induced by Irx3 ablation could partially be reversed by inhibition of sumoylation. Conclusions Our study has uncovered IRX3 as a novel upstream regulator of sumoylation, and a potent controller of epigenetic regulators, both directly and indirectly via suppressing global sumoylation levels. This study indicates that the FTO locus promotes obesity via IRX3-mediated suppression of sumoylation, which promotes adipogenic commitment and differentiation through epigenetic programming.
2025-05-29 | GSE278972 | GEO
Project description:Transcriptional profiling of E15.5 whole kidneys with a conditional deletion of Irx3/5 in the nephron progenitor cell lineage. Irx3/5 were conditionally deleted using Six2-driven Cre-recombinase. Data will provide novel insight into the functional contributions of Irx3/5 towards nephrogenesis.
2024-07-23 | GSE271904 | GEO
Project description:The Iroquois homeodomain transcription factor gene IRX3 is highly expressed in the developing nervous system, limb buds and heart. In adults, expression levels specify risk of obesity. We now report a significant functional role for IRX3 in human acute leukemia. While transcript levels are very low in normal human bone marrow cell populations, high level IRX3 expression is observed in ~30% of patients with acute myeloid leukemia (AML), ~50% of patients with T-acute lymphoblastic leukemia and ~20% of patients with B-acute lymphoblastic leukemia, typically in association with high levels of HOXA9. Expression of IRX3 alone was sufficient to immortalise murine bone marrow stem and progenitor cells, and induce T- and B-lineage leukemias in vivo with incomplete penetrance. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine bone marrow stem and progenitor cells substantially enhanced the morphologic and phenotypic differentiation block of the resulting AMLs by comparison with Hoxa9-only leukemias, through suppression of a myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 modulates the cellular consequences of HOX gene expression to enhance differentiation block in human AML.
2018-01-15 | GSE97450 | GEO
Project description:To determine Irx3 and Irx4 regulatory pathways during heart compaction, RNA-seq analyses on WT, Irx3KO, Irx4KO, and Irx3;Irx4DKO mutants hearts were performed to determine misregulated pathways upon the loss of these transcription factors. Our analyses revealed that there are overlapping functions between Irx3 and Irx4, and that both Irx3 and Irx4 are required for the regulation of the BMP/TGFβ signalling pathway known to be involved in endocardial cushion formation.
2026-05-01 | GSE114872 | GEO
Project description:The limited regenerative capacity of the adult human heart makes human induced pluripotent stem cell (hiPSC)-based therapies a promising approach for treating myocardial infarction. However, hiPSC-derived cardiomyocytes (hiPSC-CM) display immature features. In this study, we demonstrate that depletion of the transcription factor IRX3 promotes early cardiac commitment and enhances the maturation of hiPSC-CMs. We first established the temporal expression of IRX3 during hiPSC-CM differentiation and subsequently investigated its role by generating two IRX3 mutant hiPSC lines. IRX3-depleted cardiac progenitors exhibited increased expression of GATA4, NKX2-5, TBX5 and Wnt signaling-related genes, along with increased proliferation. Differentiation of IRX3-depleted cells yielded more cardiomyocytes with enhanced expression of TNNI1 and CX43. Notably, IRX3-depleted cardiomyocytes showed improved sarcomere alignment, enhanced cell-to-cell communication, and electrophysiological maturation. Furthermore, in silico analysis suggests that IRX3 regulates cardiomyocyte differentiation by modulating TBX5, GATA4 and NKX2-5 transcription along with their targets. Collectively, our findings underscore the potential of IRX3 depletion in facilitating the molecular and functional development of human cardiomyocytes.
2026-03-28 | GSE262776 | GEO
Project description:Analysis of the roles of Irx3 and Irx5 transcription factors in mouse heart development and postnatal heart function. Results show that show that Irx3 and Irx5 have redundant function in the in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation. A postnatal deletion of Irx3 and Irx5 surprisingly results in a restoration of the repolarization gradient that is altered in Irx5 mutant hearts, suggesting a model whereby postnatal Irx3 activity is normally repressed by Irx5.
2012-06-20 | GSE38826 | GEO
Project description:The Iroquois homeobox transcription factor Irx3 is associated with metabolic and hematologic disorders, but its role in cardiac repair after myocardial infarction (MI) remains unclear. This study found that Irx3 expression is significantly downregulated in the hearts of wild-type mice post-MI and in human AC16 cardiomyocytes under oxygen-glucose deprivation (OGD) conditions. Overexpression of Irx3 improved cardiac function, reduced infarct size and myocardial fibrosis, attenuated inflammatory cell infiltration, prolonged survival in MI mice, and suppressed collagen synthesis and proinflammatory cytokine secretion in vitro. Mechanistically, Irx3 directly targets Srpx2 and Ppm1l: it downregulates Srpx2 to enhance AP-1 activity, increase SMAD7 expression, and inhibit TGF-β/SMAD signaling to limit fibrosis; it upregulates Ppm1l to interact with IKKβ, suppress NF-κB signaling, and reduce inflammatory cytokines (IL-1β, IL-6, TNF-α). RNA sequencing (RNA-seq) of mouse left ventricular tissues and Irx3-overexpressing AC16 cells identified differentially expressed genes enriched in extracellular matrix (ECM) remodeling and inflammation-related pathways, confirming Irx3’s coordinate regulation of profibrotic and proinflammatory pathways. These findings highlight Irx3 as a promising therapeutic target for post-MI cardiac repair and functional recovery.
2026-02-16 | GSE319045 | GEO