Atrial Identity Is Determined by A COUP-TFII Regulatory Network (ChIP-Seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE46497 | GEO | 2013/06/07
SECONDARY ACCESSION(S): PRJNA200659
REPOSITORIES: GEO
Similar Datasets
Project description:Embryonic cardiomyocytes possess the plasticity to choose between atrial and ventricular fates. For a limited window of time, the transcription factor COUP-TFII (Nr2f2) sufficiently and essentially confers the atrial identity through direct and indirect regulation of nearly half of chamber specific genes. Examination of COUP-TFII binding sites in embryonic artia
2013-06-07 | E-GEOD-46497 | biostudies-arrayexpress
Project description:Recent studies demonstrated that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts induced augmented glycolysis and production of alpha smooth muscle actin (αSMA) and collagen1. Knockout of COUP-TFII decreased glycolysis and collagen1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1α. Overexpression of COUP-TFII reduced the cellular level of PGC1α. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.
2021-04-27 | PXD024035 | Pride
Project description:Here, we targeted mCherry to the COUP-TFII genomic locus in NKX2.5eGFP/+ hPSCs. Upon differentiation to atrial and ventricular cardiomyocytes (CMs) this dual atrial COUP-TFIImCherry/+-NKX2.5eGFP/+ reporter line allowed identification and selection of GFP+ (G+)/mCherry+ (M+) CMs following cardiac differentiation. These cells exhibited transcriptional and functional properties of atrial CMs, whereas G+/M- CMs displayed ventricular characteristics. Via CRISPR/Cas9-mediated knockout, we demonstrated that COUP-TFII is not required atrial specification in hPSCs.
2017-12-31 | GSE100199 | GEO
Project description:Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules. We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria.
2013-06-07 | GSE46496 | GEO
Project description:Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules. We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria. We extracted RNA from mutant right atria, control right atria and control ventricles from 2 months old adult mice, followed by gene expression profiling using Affymetrix microarrays.
2013-06-07 | E-GEOD-46496 | biostudies-arrayexpress
Project description:COUP-TFII (NR2F2) is expressed in somatic cells in fetal ovary. To investigate the function of COUP-TFII , we used Cre-flox model to ablate Coup-tfII in the fetal ovaries We performed microarray to compare gene expression profile between control and knockout ovaries.
2018-01-12 | GSE100015 | GEO
Project description:ChickenM-BM- ovalbumin upstream promoter-transcription factor II (COUP-TFII; NR2F2) is an orphan nuclear receptor involved in cell-fate specification, organogenesis, angiogenesis and metabolism. Ablation of COUP-TFII in the mouse uterus causes infertility due to defects in embryo attachment and impaired uterine stromal cell decidualization. Although the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown. To better elucidate the mechanisms with which COUP-TFII regulates target gene transcription, genome-wide COUP-TFII binding sites in human endometrial stromal cells (HESC) treated with deciduogenic hormones were identified using ChIP-seq. A total of 16,298 intervals (binding regions) for COUP-TFII were identified compared with the input in HESC chromatin with a very low false discovery rate (0.17%) using a stringent cutoff of p =1x10-10. Distribution of intervals showed that more than half (58.6%) of the COUP-TFII binding sites are located within 10 kb of gene boundaries. 7.5% of total intervals reside within the 10 kb promoter region. A total of 6,077 unique genes were identified to have COUP-TFII binding sites within 10 kb of their gene boundaries. Examination of NR2F2 binding in pooled primary human endometrial stromal cells from 6 healthy women upon decidualization with a hormone cocktail of cAMP, E2 and medroxyprogesterone acetate.
2013-11-02 | E-GEOD-52008 | biostudies-arrayexpress
Project description:Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII; NR2F2) is an orphan nuclear receptor involved in cell-fate specification, organogenesis, angiogenesis and metabolism. Ablation of COUP-TFII in the mouse uterus causes infertility due to defects in embryo attachment and impaired uterine stromal cell decidualization. Although the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown. To better elucidate the mechanisms with which COUP-TFII regulates target gene transcription, genome-wide COUP-TFII binding sites in human endometrial stromal cells (HESC) treated with deciduogenic hormones were identified using ChIP-seq. A total of 16,298 intervals (binding regions) for COUP-TFII were identified compared with the input in HESC chromatin with a very low false discovery rate (0.17%) using a stringent cutoff of p =1x10-10. Distribution of intervals showed that more than half (58.6%) of the COUP-TFII binding sites are located within 10 kb of gene boundaries. 7.5% of total intervals reside within the 10 kb promoter region. A total of 6,077 unique genes were identified to have COUP-TFII binding sites within 10 kb of their gene boundaries.
2013-11-02 | GSE52008 | GEO
Project description:The orphan nuclear receptor COUP-TFII is expressed at a low level in adult tissues, but its expression is increased and shown to promote progression of multiple diseases including prostate cancer, heart failure and muscular dystrophy. Suppression of COUP-TFII slows disease progression, making it an intriguing therapeutic target. Here, we identified a potent and specific COUP-TFII inhibitor through high-throughput screening. The inhibitor specifically suppressed COUP-TFII activity to regulate its target genes.
2020-05-12 | GSE142475 | GEO
Project description:Increased COUP-TFII levels are found in human dilated cardiomyopathy as well as in mouse models that develop cardiomyopathy. COUP-TFII overexpression in adult mouse hearts caused ventricular dilation and compromised cardiac functions. To gain insights on COUP-TFII’s effect in hearts, we identified the molecular profile of COUP-TFII overexpressing hearts through microarray analysis. The result may shred light on molecular mechanisms that mediate development of dilated cardiomyopathy.
2015-07-24 | GSE63759 | GEO