Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reinstatement of developmental stage-specific GATA4 enhancers controls the gene expression program in heart disease

ABSTRACT: Through integration of GATA4 genome-wide occupancy and RNA-seq dataset in embryonic conditional knockout heart, we identified a class of the master cardiac regulator GATA4 bound enhancers. With combinatorial assembly of chromatin signatures, we further refined that a unique type of fetal distal GATA4 enhancers enriched for H3K27ac, H3K4me1, but not for H3K4me3 and RNA polymerase II, are reinstated in adult hypertrophic heart. Study Gata4 and histone modifications in E12.5, Adult, Banding and Sham, and to correlate to gene expression and heart function

ORGANISM(S): Mus musculus

SUBMITTER: Fei Gu

PROVIDER: E-GEOD-52123 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Interrogating translating RNAs and cell-type specific gene expression using Cre-activated translating ribosome affinity purification

Project description:We characterize a Cre-activated TRAP allele (Rosa26fsTRAP) to show that endothelium-specific activation of Rosa26fsTRAP identifies endothelial cell enriched transcripts, and that cardiomyocyte-restricted TRAP is a useful means to identify genes that are differentially expressed in cardiomyocytes in a disease model. We also show that TRAP is an effective means to study translational regulation, and we several nuclear-encoded mitochondrial genes are under strong translational control. These RNA-seq data show that the TRAP strategy and the Rosa26fsTRAP allele will be useful tools to probe cell type specific transcriptomes, and to study translational regulation. Study TRAP RNA and total RNA in two cases: heart specific tissues, Banding or Sham, using RNA-seq technology.

2013-08-20 | E-GEOD-45152 | biostudies-arrayexpress

Reinstatement of developmental stage-specific GATA4 enhancers controls the gene expression program in heart disease

Project description:Through integration of GATA4 genome-wide occupancy and RNA-seq dataset in embryonic conditional knockout heart, we identified a class of the master cardiac regulator GATA4 bound enhancers. With combinatorial assembly of chromatin signatures, we further refined that a unique type of fetal distal GATA4 enhancers enriched for H3K27ac, H3K4me1, but not for H3K4me3 and RNA polymerase II, are reinstated in adult hypertrophic heart.

2014-08-13 | GSE52123 | GEO

Pi3kcb links Hippo-YAP and PI3K-AKT signaling pathways to promote cardiomyocyte proliferation and survival

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-02-20 | E-GEOD-57719 | biostudies-arrayexpress

Integration of Protein Interactome Data with Congenital Heart Disease Variants Reveals Disease Genes

Project description:Congenital Heart Disease (CHD) accounts for 1% of birth defects, and while large-scale genetic studies have uncovered genes associated with CHDs, identifying causal mutations remains a challenge. We hypothesized that genetic determinants for CHDs could be found in the protein interactomes of GATA4 and TBX5, two cardiac transcription factors (TFs) associated with CHDs. Defining their interactomes in human cardiac progenitors via affinity purification-mass spectrometry and integrating the results with genetic data from the Pediatric Cardiac Genomic Consortium (PCGC) revealed an enrichment of de novo variants among proteins that interact with GATA4 or TBX5. A consolidative score designed to prioritize TF interactome members based on distinctive variant, gene and proband features identified numerous likely CHD-causing genes, including the epigenetic reader GLYR1. GLYR1 and GATA4 widely co-occupied cardiac developmental genes resulting in co-activation and the GLYR1 variant associated with CHD disrupted interaction with GATA4. This integrative proteomic and genetic approach provides a framework for prioritizing and interrogating the contribution of genetic variants in CHD and can be extended to other genetic diseases.

2022-07-05 | PXD022091 | Pride

A genome-wide screen identifies silencers with distinct chromatin properties and mechanisms of repression

Project description:Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs), enhancers and silencers. While enhancers have been thoroughly characterized, the properties and mechansisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs, as they mostly lack detectable DNA accessibility. The silencer-binding TF CG11247, which we term Saft, safeguards cell fate decisions in vivo and functions via a highly-conserved domain we term ZAC and the corepressor G9a, independently of G9a’s H3K9-methyltransferase activity. Overall, our identification of silencers with unexpected properties and mechanisms has important implications for the understanding and future study of repressive CREs, as well as the functional annotation of animal genomes.

2024-11-13 | PXD048161 | Pride

Genome-wide occupancy profile of Tbx3, Gata4, Nkx2-5 and p300 in adult mouse whole heart

Project description:The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers. Here, we assessed the genome-wide occupation of conduction system–regulating transcription factors TBX3, NKX2-5, and GATA4 and of enhancer-associated coactivator p300 in the mouse heart, uncovering cardiac enhancers throughout the genome. Examination of 3 cardiac transcription factors and p300 in adult mouse heart

2012-06-22 | E-GEOD-35151 | biostudies-arrayexpress

Hierarchical enhancers 1 confer the temporal and partially compensatory transcriptional regulation of Nkx2-5 during heart development

Project description:We comprehensively interrogate enhancers U1 and U2 in controlling Nkx2-5 transcription during heart development. Serial genomic deletions in mice reveal a functional hierarchy of U1 and U2 as evidenced by stage-dependent phenotypic variations. Specifically, U1 and U2 function redundantly to confer Nkx2-5 expression at early stages, but U2 instead of U1 supported its expression at later stages of heart chamber formation and maturation. Combined deletions markedly reduce Nkx2-5 dosage as early as E7.5, despite being largely reinstated two days later, displaying heart malformations with precocious differentiation of cardiac progenitors. Together, we propose a model that the temporal and partially compensatory regulatory function of two enhancers dictates a TF?s dosage and specificity during development.

2022-07-03 | GSE133760 | GEO

4C Sequencing using the Fos gene promoter and enhancers as viewpoints in mouse hindbrain cells at different time points during development

Project description:Measuring contacts between the Fos gene promoter and enhancers in developing mouse hindbrain cells

2021-01-09 | E-MTAB-8295 | biostudies-arrayexpress

Transcription profiling of hearts from mice heterozygous for Gata4 mutation (G4D) to investigate the significance of Gata4 in regulating postnatal heart function and in regulating the hypertrophic response of the heart to pathological stress.

Project description:An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiac cardiomyocytes, the transcription factor Gata4 is required for agonist-induced cardiomyocyte hypertrophy. We hypothesized that in the intact organism Gata4 is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of Gata4 (G4D). At baseline, G4D mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC), G4D mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls, G4D-TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed upregulation of genes associated with apoptosis and fibrosis, including members of the TGF? pathway. Our data demonstrate that Gata4 is essential for cardiac function in the postnatal heart. After pressure overload, Gata4 regulates the pattern of cardiomyocyte hypertrophy and protects the heart from load-induced failure. Experiment Overall Design: We reasoned that if Gata4 was a crucial regulator of pathways necessary for cardiac hypertrophy, then modest reductions of Gata4 activity should result in an observable cardiac phenotype. To test this hypothesis, we used gene targeted mice that express reduced levels of Gata4. We characterized these mice at baseline and after pressure Experiment Overall Design: overload.

2007-11-13 | E-GEOD-5500 | biostudies-arrayexpress

Genome-wide occupancy profile of Tbx3, Gata4, Nkx2-5 and p300 in adult mouse whole heart

2012-06-22 | GSE35151 | GEO