Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

49 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of the mouse heart transcriptome by Celf1

ABSTRACT: The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the heart. Mice were engineered to express the reverse tetracycline trans-activator (rtTA) from a heart-specific alpha myosin heavy chain promoter, and an N-terminal Flag-tagged version of the LYLQ isoform of human Celf1 from a tet-inducible promoter. Mice were fed doxycycline to induce Celf1 expression in heart, and hearts were harvested from 3 mice each at 12 hour, 24 hour, 72 hour, and 7 day time points. To account for potential doxycycline-dependent effects, control mice were fed doxycycline for 72 hours but these mice did not contain the tet-inducible Celf1 cassette. In total, 15 hearts were analyzed by RNA-Seq.

ORGANISM(S): Mus musculus

SUBMITTER: Eric Wang

PROVIDER: E-GEOD-56185 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Transcriptome modulation of ventricles, cardiomyocytes and cardiac fibroblasts during postnatal mouse development

Project description:During development the fetal heart undergoes a rapid and dramatic transition to adult function through transcriptional and post-transcriptional mechanisms, including alternative splicing (AS). We performed deep RNA-sequencing for high-resolution analysis of transcriptome changes during postnatal mouse heart development using RNA from ventricles and freshly isolated cardiomyocytes (CM) and cardiac fibroblasts (CF). Extensive changes in gene expression and AS occur primarily between postnatal days 1 and 28. CM and CF showed reciprocal regulation of gene expression during postnatal development reflecting differences in proliferative capacity, cell adhesion functions, and mitochondrial metabolism. We found that AS plays a novel role in vesicular trafficking and membrane organization during postnatal CM development. Interestingly, these AS transitions are enriched among targets of two RNA-binding proteins, Celf1 and Mbnl1, which undergo developmentally regulated change in expression. Vesicular traffic genes affected by AS during normal development where Celf1 is down-regulated, showed a reversion to neonatal AS patterns when Celf1 was over-expressed in adults. RNA-seq was performed in RNA samples of ventricles, cardiomyocytes or cardiac fibroblast at different developmental stages; embryonic day 17, postnatal day (PN) 1, 10, 28 and 90 for ventricles, PN1-3, PN28 and PN60 for cardiac fibroblasts, and PN1-2, PN30, and PN67 for cardiomyocytes

2014-04-16 | E-GEOD-49906 | biostudies-arrayexpress

Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1

Project description:The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development. RNA-sequencing of mRNA from homozygous neonatal hearts identified a network of cell cycle genes significantly up-regulated and down-regulation of ion transport and circadian genes. Cell cycle genes are enriched for Celf1 binding sites supporting a regulatory role in mRNA stability of these transcripts. We also identified a cardiac splicing network coordinated by Celf1 depletion. Target events contain multiple Celf1 binding sites and enrichment in GU-rich motifs. Identification of direct Celf1 targets will advance our knowledge in the mechanisms behind developmental networks regulated by Celf1 and diseases where Celf1 is mis-regulated.

2016-10-22 | GSE85646 | GEO

Regulation of the mouse heart transcriptome by Celf1

Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the heart.

2014-04-01 | GSE56185 | GEO

Whole heart response to stable HIF-1alpha overexpression

Project description:An oxygen stable form of HIF-1alpha was overexpressed in the hearts of mice, under tet-off control. Bi-allelic transgenic mice were created by crossing alpha-MHC promoter/tet transactivating protein expressing mice with tet responsive element promter/stable HIF-1alpha protein expressing mice. Mice were either, maintained on Doxycycline (inhibiting the expression of the HIF-1alpha transgene) or removed from doxycycline (inducing expression) for one or three days.

2010-05-15 | E-GEOD-12673 | biostudies-arrayexpress

OPLAH prevents accumulation of cardiotoxic 5-oxoproline after ischemic injury and improves cardiac function

Project description:In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and adult mice with HF. Our screen identified 5-oxoprolinase (OPLAH), a member of the -Glutamyl cycle, that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients we observed elevated plasma 5-oxoproline levels, which were associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential novel diagnostic, prognostic and therapeutic options in HF.

2017-11-08 | E-MTAB-5449 | biostudies-arrayexpress

Functional Antagonism Between CELF and Mbnl Proteins in Cytoplasm and Nucleus [hearts]

2014-12-01 | GSE61891 | GEO

Functional Antagonism Between CELF and Mbnl Proteins in Cytoplasm and Nucleus [muscle]

2014-12-01 | GSE61890 | GEO

Role of cellular retinol-binding protein, type 1 and retinoid homeostasis in the adult mouse heart: a multi-omic approach

Project description:The main active metabolite of Vitamin A, all-trans retinoic acid (RA), is responsible for proper cellular function and tissue organization. The role of RA has been extensively studied in development, but there is limited research on its role in the adult heart. Cellular retinol-binding protein, type 1 (CRBP1), encoded by retinol-binding protein, type 1 (Rbp1), regulates RA homeostasis by delivering vitamin A to enzymes for RA synthesis. An animal model of CRBP1 deficiency, such as Rbp1–/– mice, can provide insight into disrupted RA biosynthesis and signaling. In this work, a multi-omics approach was used to characterize the effect of CRBP1 loss. Retinoid homeostasis was disrupted in Rbp1-/- mouse heart tissue, as seen by a 33% and 24% decrease in RA levels in the left and right ventricles, respectively, compared to wild-type mice (WT). To further inform on the effect of disrupted RA homeostasis, we conducted high-throughput targeted metabolomics. A total of 222 metabolite and metabolite combinations were analyzed, with 33 having differential expression between Rbp1-/- and WT hearts. Additionally, we performed global proteome profiling to further characterize the impact of CRBP1 loss in adult mouse hearts. More than 2,606 unique proteins were identified, with 340 proteins having differential expression between Rbp1-/- and WT hearts. Pathway analysis performed on metabolomic and proteomic data revealed pathways related to cellular metabolism and cardiac metabolism were the most disrupted in Rbp1-/- mice. Together, these studies provide data for establishing the effect of dysregulated RA signaling in the adult mouse heart.

2022-10-13 | PXD029349 | Pride

Myotonic dystrophy type 1 (DM1) leads to altered mRNA expression in heart tissue

Project description:Myotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes. We identified transcripts over-expressed or under-expressed in hearts of wildtype adult mice, wildtype embryonic day 14 (E14), and DM1 mice induced to express CUGexp RNA for 72h and 1wk, when compared to MCM controls. Multiple group comparison.

2014-01-24 | E-GEOD-48991 | biostudies-arrayexpress

Microarray analysis of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposed Amputated Adult Zebrafish Heart Ventricles

Project description:The purpose of this experiment is to understand which transcripts are differentially expressed following exposure to TCDD. We used microarrays to understand global changes in gene signal intensity Adult zebrafish (danio rerio) were injected (i.p) to vehicle control or TCDD (70 ng/g) one day prior to heart ventricle amputation. A subset of fish were exposed but the hearts were not amputated. Amputated hearts were collected at 6 hours post amputation and 7 days post amputation and processed for microarray analysis

2011-11-29 | E-GEOD-33981 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data