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SRP045678
Saccharomyces cerevisiae
18 Downloadable Samples
Illumina HiSeq 2000
Description
Gene expression levels are determined by the balance between rates of mRNA transcription and decay, and genetic variation in either of these processes can result in heritable differences in transcript abundance. Although the genetics of gene expression has been the subject of intense interest, the contribution of heritable variation in mRNA decay rates to gene expression variation has received far less attention. To this end, we developed a novel statistical framework and measured allele-specific differences in mRNA decay rates in a diploid yeast hybrid created by mating two genetically diverse parental strains. In total, we estimate that 31% of genes exhibit allelic differences in mRNA decay rate, of which 350 can be identified at a false discovery rate of 10%. Genes with significant allele-specific differences in mRNA decay rate have higher levels of polymorphism compared to other genes, with all gene regions contributing to allelic differences in mRNA decay rate. Strikingly, we find widespread evidence for compensatory evolution, such that variants influencing transcriptional initiation and decay having opposite effects, suggesting steady-state gene expression levels are subject to pervasive stabilizing selection. Our results demonstrate that heritable differences in mRNA decay rates are widespread, and are an important target for natural selection to maintain or fine-tune steady-state gene expression levels. Overall design: We measured rates of allele-specific mRNA decay (ASD) in a diploid yeast produced by mating two genetically diverse haploid Saccharomyces cerevisiae strains: the laboratory strain BY4716 (BY), which is isogenic to the reference sequence strain S288C, and the wild Californian vineyard strain RM11-1a (RM). Briefly, we introduced rpb1-1, a temperature sensitive mutation in an RNA polymerase II subunit, to each of the haploid yeast strains, mated the strains, and grew the resulting hybrid diploid to mid-log phase at 24 °C, before rapidly shifting the culture to 37 °C to inhibit transcription. RNA-seq was performed on culture samples taken at 0, 6, 12, 18, 24, and 42 minutes subsequent to the temperature shift. To identify ASD, we used transcribed polymorphisms to distinguish between parental transcripts, and compared the relative levels of transcript abundance over the time course. Note, this experimental design internally controls for trans-acting regulatory variation as well as environmental factors. Under the null hypothesis of no ASD, the proportion of reads from the BY transcript (p_BY = N_BY / (N_BY + N_RM)) observed over the time course remains unchanged. However, genes with ASD will exhibit an increasing or decreasing proportion of BY reads as a function of time. In total, we measured ASD from three independent biological replicates.
Publication Title
Heritable variation of mRNA decay rates in yeast.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Mus musculus
- 267 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 134 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse genetic crosses were established between the PyMT model of metastatic breast cancer and MOLF/Ei strain. Tumors were harvested from the animals for gene expression analysis to identify genes associated with progression to distant metastatic disease.
Publication Title
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 133 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse genetic crosses were established between the PyMT model of metastatic breast cancer and the G5 generation of the Diversity Outcross (DO). Tumors were harvested from the animals for gene expression analysis to identify genes associated with progression to distant metastatic disease.
Publication Title
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
Expression profiling of hepatocytes-derived ductal cells with properties intermediate between mature hepatocytes and cholangiocytes Overall design: Chimeric adult mice were generated where mature hepatocytes were marked with a fluorescent red marker. Chronic injury was induced for ~6weeks and three cell types were isolated by FACS (Influx, BD) for expression analysis by RNAseq based on cell surface phenotype and origin: hepatocytes (n=3), hepatocyte-derived oval cells (1c3+, n=5), and cholangiocyte-derived oval cells (1c3+, n=5).
Publication Title
Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcriptional control is dependent on a vast network of epigenetic modifications. One epigenetic mark of particular interest is tri-methylation of lysine 27 on histone H3 (H3K27me3), which is catalyzed and maintained by the Polycomb Repressor Complex (PRC2). Although this histone mark is studied widely, the precise relationship between its local pattern of enrichment and regulation of gene expression is currently unclear. We have used ChIP-seq to generate genome wide maps of H3K27me3 enrichment, and have identified three enrichment profiles with distinct regulatory consequences. First, a broad domain of H3K27me3 enrichment across the body of genes corresponds to the canonical view of H3K27me3 as inhibitory to transcription. Second, a peak of enrichment around the transcription start site is commonly associated with bivalent genes, where H3K4me3 also marks the TSS. Finally and most surprisingly, we identified an enrichment profile with a peak in the promoter of genes that is associated with active transcription. Genes with each of these three profiles were found in different proportions in each of the cell types studied. The data analysis techniques developed here will be useful for the identification of common enrichment profiles for other histone modifications that have important consequences for transcriptional regulation.
Publication Title
ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Promoter 1.0R Array (hsprompr)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-β in human breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Promoter 1.0R Array (hsprompr)
Description
TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. Our goal was to use integrated genomic approaches in a model of human breast cancer progression to identify core TGF-beta-regulated genes that specifically reflect the tumor suppressor activity of TGF-beta. The model consisted of the non-tumorigenic MCF10A (M1), the premalignant MCF10AT1k.cl2 (M2), the early malignant MCF10Ca1h (M3) and the highly malignant, metastatic MCF10Ca1a.cl1 (M4) cell lines. We have previously shown that tumor suppressor activity of TGF-beta is lost in the highly malignant M4 cells.
Publication Title
An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-β in human breast cancer.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Promoter 1.0R Array (hsprompr), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. We have previously shown that TGF-beta has tumor suppressor activity in the MCF10Ca1h (M3) human breast cancer xenograft model. To identify potential molecular players in the tumor suppressor responses, we performed global gene expression analyses.
Publication Title
An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-β in human breast cancer.
Sample Metadata Fields
Specimen part, Treatment
View Samples