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GSE6210
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc1beta gene (PGC1beta E3,4-/E3,4- mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERRalpha, a major target of PGC1beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC1beta mutant mice have normal skeletal muscle response to insulin, but have hepatic insulin resistance. These results demonstrate that PGC1beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver.
Publication Title
Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Objective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range.
Publication Title
Liver adapts mitochondrial function to insulin resistant and diabetic states in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
IlluminaHiSeq2500
Description
The human nuclear poly(A)-binding protein PABPN1 has been implicated in the decay of nuclear noncoding RNAs (ncRNAs). In addition, PABPN1 stimulates hyperadenylation by poly(A) polymerase, and this activity is thought to be required for decay. Here, we inactivated hyperadenylation by two distinct mechanisms and examined changes in gene expression in HEK293 cells by RNAseq. We observed the upregulation of various ncRNAs, including snoRNA host genes, primary miRNA transcripts, and upstream antisense RNAs, confirming that hyperadenylation is broadly required for the degradation of PABPN1-targets. In addition, we found that mRNAs with retained introns are susceptible to PABPN1 and PAPa/?-mediated decay (PPD). Transcripts are targeted for degradation due to inefficient export, which is a consequence of reduced intron number or incomplete splicing. We conclude that PPD is an important mammalian nuclear RNA decay pathway for the removal of poorly spliced and nuclear-retained transcripts. Overall design: Poly(A)+ RNA from HEK293 cells was analyzed by next generation sequencing following depletion of PAPa and PAP? or expression of a dominant negative allele of PABPN1 (LALA) designed to inhibit polyadenylation. For each condition, we collected both total RNA and a nuclear-enriched sample. Each sample was collected in duplicate.
Publication Title
Canonical Poly(A) Polymerase Activity Promotes the Decay of a Wide Variety of Mammalian Nuclear RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
The RING domain protein Arkadia/RNF111 is a ubiquitin ligase in the transforming growth factor beta (TGFß) pathway. We previously identified Arkadia as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). However, precisely how SUMO interaction contributes to the function of Arkadia was not resolved. Through analytical molecular and cell biology, we found that the SIMs share redundant function with Arkadia''s M domain, a region distinguishing Arkadia from its paralogs ARKL1/ARKL2 and the prototypical SUMO-targeted ubiquitin ligase (STUbL) RNF4. The SIMs and M domain together promote both Arkadia''s colocalization with CBX4/Pc2, a component of Polycomb bodies, and the activation of a TGFbeta pathway transcription reporter. Transcriptome profiling through RNA sequencing showed that Arkadia can both promote and inhibit gene expression, indicating that Arkadia''s activity in transcriptional control may depend on the epigenetic context, defined by Polycomb repressive complexes and DNA methylation [Sun, Liu, and Hunter (2014) Mol Cell Biol 34(16):2981-2995]. Overall design: To determine the role of Arkadia in TGFß signaling at the transcriptome level, the profiles of TGFß-stimulated gene expression were examined in Ark+/+ (Ark_WT), Ark-/- (Ark_null), and Arkadia (WT and sim mutant)-reconstituted Ark-/- MEFs. RNA sequencing was carried out using poly(A)-enriched RNA samples from unstimulated cells and cells treated with TGFß for 1h, 4h, or 16h as indicated. Two batches of sequencing data for a total of 16 independent samples were submitted.
Publication Title
Multiple Arkadia/RNF111 structures coordinate its Polycomb body association and transcriptional control.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. Overall design: Determine changes in gene expression levels between WT and DAXX K/D prostate cancer cells by RNA-Seq (PC3 Cells).
Publication Title
The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 42 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Metastasis predictive gene signatures can result from either somatic mutation, inherited polyrmorphism or both. This experiment is designed to look at the gene expression differences due to differences in somatic mutations in the initiating oncogene, PyMT. Met1 is from a fully metastatic FVB mammary tumor cell line, DB7 contains a mutation that permits tumor formation, but suppresses metastatic ability.
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from normal tissues
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from mouse tumor tissues
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
F1 hybrids from (AKR/J x FVB/NJ) and (DBA/2J x FVB/NJ) outcrosses display a 20-fold difference in mammary tumor metastatic capacity, due to differences in inherited polymorphisms. Expression studies were performed to determine whether polymorphism-driven gene expression signatures predictive of outcome could be generated from normal tissues
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples