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GSE14691
Mus musculus
58 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Myotonic dystrophy type 1 (DM1) is an RNA dominant disease in which mutant transcripts containing an expanded CUG repeat (CUGexp) cause muscle dysfunction by interfering with biogenesis of other mRNAs. The toxic effects of mutant RNA are mediated partly through sequestration of splicing regulator Muscleblind-like 1 (Mbnl1), a protein that binds to CUGexp RNA. A gene that is prominently affected encodes chloride channel 1 (Clcn1), resulting in hyperexcitability of muscle (myotonia). To identify DM1-affected genes and study mechanisms for dysregulation, we performed global mRNA profiling in transgenic mice that express CUGexp RNA, as compared to Mbnl1 knockout and Clcn1 null mice. We found that the majority of changes induced by CUGexp RNA in skeletal muscle can be explained by reduced activity of Mbnl1, including many changes that are secondary to myotonia. The pathway most affected comprises genes involved in calcium signaling and homeostasis. Some effects of CUGexp RNA on gene expression are caused by abnormal alternative splicing or downregulation of Mbnl1-interacting mRNAs. However, several of the most highly dysregulated genes showed altered transcription, as indicated by parallel changes of the corresponding premRNAs. These results support the idea that trans-dominant effects of CUGexp RNA on gene expression in this transgenic model may occur at the level of transcription, RNA processing, and mRNA decay, and are mediated mainly but not entirely through sequestration of Mbnl1.
Publication Title
Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The LIM-only protein FHL2 acts as a transcriptional modulator that positively or negatively regulates multiple signaling pathways. We recently reported that FHL2 cooperates with CBP/p300 in the activation of -catenin/TCF target gene cyclin D1. In this paper, we demonstrate that FHL2 is associated with the cyclin D1 promoter at the TCF/CRE site, providing evidence that cyclin D1 is a direct target of FHL2. We show that deficiency of FHL2 greatly reduces the proliferative capacity of spontaneously immortalized mouse fibroblasts which is associated with decreased expression of cyclin D1 and p16INK4a, and hypophosphorylation of Rb. Reexpression of FHL2 in FHL2-null fibroblasts efficiently restores cyclin D1 levels and cell proliferative capacity, indicating that FHL2 is critical for cyclin D1 activation and cell growth. Moreover, ectopic cyclin D1 expression is sufficient to override growth inhibition of immortalized FHL2-null fibroblasts. Gene expression profiling revealed that FHL2 deficiency triggers a broad change of the cell cycle program that is associated with downregulation of several G1/S and G2/M cyclins, E2F transcription factors and DNA replication machinery, thus correlating with reduced cell proliferation. This change also involves downregulation of the negative cell cycle regulators, particularly INK4 inhibitors, which could counteract the decreased expression of cyclins, allowing cells to grow. Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation.
Publication Title
The LIM-only protein FHL2 regulates cyclin D1 expression and cell proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HiSeq 2000
Description
We transfected PC3 cells with 100nM of a scrambled antisense oligonucleotide (AON) and an AON directed against MBNL1 exon 7 (36 basepairs) in order to skip the latter. Cells were harvested at 72h post-transfection and RNAseq was performed with ribozero depletion. Overall design: For RNA-Seq library preparation we followed the Illumina TruSeq RNA Sample Preparation Kit v2 manual. At least 70 million, 75bp long paired end reads were mapped to the GRCh37/hg19 version of the human genome per replicate using STAR 2.4.2a (doi: 10.1093/bioinformatics/bts635) using the default parameters.
Publication Title
MBNL1 alternative splicing isoforms play opposing roles in cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- NextSeq 500, Illumina Genome Analyzer IIx
Description
Microsatellite expansions often occur in non-coding regions of the genome. In this study, we test their effect on host transcript RNA processing. Overall design: RNA-seq on affected tissues and peripheral blood from control and affected patients.
Publication Title
Intron retention induced by microsatellite expansions as a disease biomarker.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Misregulated alternative splicing appears to be a major factor in the pathogenesis of myotonic dystrophy. The present study was done to further explore alternative splicing in this condition by doing exon-level analysis of mRNA from skeletal muscle of 8 subjects with type 1 myotonic dystrophy, 7 subjects with type 2 myotonic dystrophy, 8 disease controls (subjects with facioscapulohumeral muscular dystrophy), and 8 healthy controls . The ratios of signals from the various exons of a gene provided an index of altered exon inclusion/exclusion that was independent of the overall expression of that gene. There were numerous transcripts for which there was evidence of abnormal alternative splicing in subjects with myotonic dystrophy. For many of these transcripts, the abnormal splicing was confirmed by an independent RT-PCR approach.
Publication Title
Splicing biomarkers of disease severity in myotonic dystrophy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Liver RNA samples from C57BL6 mice drinking Hydrogen water for 4 weeks
Publication Title
Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles: meta-analyses of gene expression profiles.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A unique H2A histone variant occupies the transcriptional start site of active genes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Several bacterial human pathogens regulate the production of virulence factors by temperature, expressing them only at 37 C. Accordingly we show that the production of all P. aeruginosa virulence factors that are dependent on the QS transcriptional regulator RhlR, but only a fraction that are activated by LasR, are induced at 37 C compared to 30 C or 25 C. The RhlR-dependent induction at 37 C is a posttranscriptional effect due to an RNA thermometer of the ROSE family that thermoregulates the expression of rhlAB operon involved in rhamnolipids production, a virulence associated trait. This RNA structure also affects the expression of the downstream rhlR gene. A second thermometer is present upstream lasI and causes a reduced expression of this gene at lower temperatures without causing a significant decrease of the autoinducer 3-oxo-dodecanoyl homoserine lactone.
Publication Title
Regulation of Pseudomonas aeruginosa virulence factors by two novel RNA thermometers.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 1000
Description
Minocycline is a potent modulator of retinal microglia Overall design: Global mRNA expression analysis of CD1 mouse retinas in control, light damage and light damage plus minocycline conditions
Publication Title
Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Drosophila Gene 1.1 ST Array (drogene11st)
Description
Analysis of Drosophila melanogaster early embryos (pre-zygotic genome activation) following the germ line-specific depletion of the dMLL3/4 histone methyltransferase (also known as Trr). These results provide insight into the molecular mechanisms responsible for the assembly of the zygotic genome at fertilization.
Publication Title
The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization.
Sample Metadata Fields
Specimen part
View Samples