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SRP064618
Mus musculus
2 Downloadable Samples
Illumina HiSeq 2000
Description
Transcription factors (TFs) bind specific sequences in promoter-proximal and distal DNA elements in order to regulate gene transcription. RNA is transcribed from both promoter-proximal and distal DNA elements, and some DNA-binding TFs have also been shown to bind RNA. These obsevations led us to postulate that RNA transcribed from regulatory elements contributes to stable TF occupancy at these regulatory elements. We show here that the ubiquitously expressed TF YY1 binds to both proximal and distal regulatory elements and to the RNA species associated with these elements near active genes in embryonic stem cells. Inhibition of transcription from these elements reduces YY1 occupancy. In contrast, tethering of RNA species near YY1 DNA binding sites enhances YY1 occupancy. We propose that RNA acts as trap to maintain certain TFs at active enhancer and promoter-proximal regulatory elements. Thus, transcriptional control generally involves a positive feedback loop, where YY1 and other TFs stimulate local transcription, and newly transcribed nascent RNA reinforces local TF occupancy. This model helps explain why TFs occupy only the small fraction of their consensus motifs in the mammalian genome where transcription is detected. Overall design: RNA-Seq in mouse embryonic stem cells before and after knockdown of exosome protein
Publication Title
Transcription factor trapping by RNA in gene regulatory elements.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Short interfering RNAs (siRNA) are widely used as tool for gene inactivation in basic research and therapeutic applications. One of the major shortcomings of siRNA experiments are sequence-specific Off-target effects. Such effects are largely unpredictable because siRNAs can affect partially complementary sequences and function like microRNAs (miRNAs), which inhibit gene expression on mRNA stability or translational levels.
Publication Title
siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.
Sample Metadata Fields
Cell line
View Samples- Caenorhabditis elegans
- 30 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Adaptation of C. elegans to hypertonic environments involves the accumulation of the organic osmolyte glycerol via transcriptional upregulation of the glycerol biosynthestic enzyme gpdh-1. A number of mutants, termed osmotic stress resistant (osr) mutants, have been identified. osr mutants cause constitutive upregulation of gpdh-1 and confer extreme resistance to hypertonicity. We tested the hypothesis that osr mutants broadly activate a gene expression program normally activated by osmotic stress in wild type animals using Affymterix microarray analysis of the hypertonic stress response in wild type animals and of constituitive gene expression changes in five osr mutants.
Publication Title
Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: The prefrontal cortex is important in regulating sleep and mood. Diurnally regulated genes in the prefrontal cortex may be controlled by the circadian system, by the sleep-wake states, or by cellular metabolism or environmental responses. Bioinformatics analysis of these genes will provide insights into a wide-range of pathways that are involved in the pathophysiology of sleep disorders and psychiatric disorders with sleep disturbances. Results: We examined gene expression in the mouse prefrontal cortex at four time points during the 24-hour (12-hour light:12-hour dark) cycle by microarrays, and identified 3,890 transcripts corresponding to 2,927 genes with diurnally regulated expression patterns. We show that 16% of the genes identified in our study are orthologs of identified clock, clock controlled or sleep/wakefulness induced genes in the mouse liver and SCN, rat cortex and cerebellum, or Drosophila head. The diurnal expression patterns were confirmed in 16 out of 18 genes in an independent set of RNA samples. The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by the Gene Ontology classification and by the analysis of enriched transcription factor binding sites. Conclusions: Our analysis demonstrates that ~10% of transcripts have diurnally regulated expression patterns in the mouse prefrontal cortex. Functional annotation of these genes will be important for the selection of candidate genes for behavioural mutants in the mouse and for genetic studies of disorders associated with anomalies in the sleep:wake cycle and circadian rhythms.
Publication Title
Genome-wide expression profiling and bioinformatics analysis of diurnally regulated genes in the mouse prefrontal cortex.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Our results suggest that HCMV infection disrupts the self-renewal capacity of NPCs and influences their differentiation.
Publication Title
Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The retinal pigment epithelium (RPE) provides vital support to photoreceptor cells and its dysfunction is associated with the onset and progression of age-related macular degeneration (AMD). Surgical provision of RPE cells may ameliorate AMD and thus it would be valuable to develop sources of patient-matched RPE cells for this application of regenerative medicine. We describe here the generation of functional RPE-like cells from fibroblasts that represent an important step toward that goal. We identified candidate master transcriptional regulators of RPEs using a novel computational method and then used these regulators to guide exploration of the transcriptional regulatory circuitry of RPE cells and to reprogram human fibroblasts into RPE-like cells. The RPE-like cells share key features with RPEs derived from healthy individuals, including morphology, gene expression and function, and thus represent a step toward the goal of generating patient-matched RPE cells for treatment of macular degeneration.
Publication Title
A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not depend on this structural protein. Here we show that the transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements in all cells examined. YY1 forms dimers that can facilitate DNA interactions. Deletion of YY1 binding sites or depletion of YY1 can disrupt enhancer-promoter looping and normal gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control. Overall design: Single-end 40 bp Poly-A RNA-seq in mouse embryonic stem cells before and after YY1 depletion
Publication Title
YY1 Is a Structural Regulator of Enhancer-Promoter Loops.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not depend on this structural protein. Here we show that the transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements in all cells examined. YY1 forms dimers that can facilitate DNA interactions. Deletion of YY1 binding sites or depletion of YY1 can disrupt enhancer-promoter looping and normal gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control. Overall design: Single-cell RNA-seq in mouse embryonic stem cells with and without YY1 protein
Publication Title
YY1 Is a Structural Regulator of Enhancer-Promoter Loops.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Hippocamus and amygdala expression was examined in nave, conditioned stimulus exposed, and fear conditioned mice 30 minutes after behavioral manipulation
Publication Title
Differential transcriptional response to nonassociative and associative components of classical fear conditioning in the amygdala and hippocampus.
Sample Metadata Fields
No sample metadata fields
View Samples