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SRP017325
Saccharomyces cerevisiae
18 Downloadable Samples
Illumina HiSeq 2000
Description
Classic ‘position effect’ experiments repositioned genes to the telomere to demonstrate that the epigenetic landscape can dramatically alter gene expression. Here we show that systematic gene knockout collections provide an exceptional resource for interrogating position effects, not only at the telomere but at every single genetic locus. Because deleted genes are replaced by the same reporter gene, interrogation of this reporter provides a sensitive probe into many different chromatin environments while controlling for genetic context. Using this approach we find that, whereas replacement of yeast genes with the kanMX marker does not perturb the chromatin landscape, differences due to gene position account for more than 35% of marker gene activity. We observe chromatin influences different from those reported previously, including an antagonistic interaction between histone H3 lysine 36 trimethylation (H3K36me3) and the Rap1 transcriptional activation site in kanMX that is mediated through a Set2-Rpd3-dependent pathway. This interaction explains why some yeast genes have been resistant to deletion and allows successful generation of these deletion strains using a modified transformation procedure. These findings demonstrate that chromatin regulation is not governed by a uniform ‘histone code’, but by specific interactions between chromatin and genetic factors. Overall design: Data included are RNA-Seq data for 4 heterzygous diploid yeast strains and diploid wild-type. Therea re three replicates for each heterzygous strain, and six replicates for wild-type.
Publication Title
Decoupling epigenetic and genetic effects through systematic analysis of gene position.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 22 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The circadian clock generates daily rhythms in mammalian liver processes, such as glucose and lipid homeostasis, xenobiotic metabolism, and regeneration. The mechanisms governing these rhythms are not well understood, particularly the distinct contributions of the cell-autonomous clock and central pacemaker to rhythmic liver physiology. Through microarray expression profiling in MMH-D3 hepatocytes, we identified over 1,000 transcripts that exhibit circadian oscillations, demonstrating that many rhythms can be driven by the cell-autonomous clock and that MMH-D3 is a valid circadian model system. The genes represented by these circadian transcripts displayed both co-phasic and anti-phasic organization within a protein-protein interaction network, suggesting the existence of competition for binding sites or partners by genes of disparate transcriptional phases. Multiple pathways displayed enrichment in MMH-D3 circadian transcripts, including the polyamine synthesis module of the glutathione metabolic pathway. The polyamine synthesis module, which is highly associated with cell proliferation and whose products are required for initiation of liver regeneration, includes enzymes whose transcripts exhibit circadian oscillations, such as ornithine decarboxylase (Odc1) and spermidine synthase (Srm). Metabolic profiling revealed that the enzymatic product of SRM, spermidine, cycles as well. Thus, the cell-autonomous hepatocyte clock can drive a significant amount of transcriptional rhythms and orchestrate physiologically relevant modules such as polyamine synthesis.
Publication Title
Cell-autonomous circadian clock of hepatocytes drives rhythms in transcription and polyamine synthesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Macaca mulatta
- 19 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
HIV-associated dementia (HAD) is a syndrome occurring in HIV-infected patients with advanced disease that likely develops as a result of macrophage and microglial activation as well as other immune events triggered by virus in the central nervous system. The most relevant experimental model of HAD, rhesus macaques exhibiting SIV encephalitis (SIVE), closely reproduces the human disease and has been successfully used to advance our understanding of mechanisms underlying HAD. In this study we integrate gene expression data from uninfected and SIV-infected hippocampus with a human protein interaction network and discover modules of genes whose expression patterns distinguish these two states, to facilitate identification of neuronal genes that may contribute to SIVE/HIV cognitive deficits. Using this approach we identify several downregulated candidate genes and select one, EGR1, a key molecule in hippocampus-related learning and memory, for further study. We show that EGR1 is downregulated in SIV-infected hippocampus and that it can be downregulated in differentiated human neuroblastoma cells by treatment with CCL8, a product of activated microglia. Integration of expression data with protein interaction data to discover discriminatory modules of interacting proteins can be usefully employed to prioritize differentially expressed genes for further study. Investigation of EGR1, selected in this manner, indicates that its downregulation in SIVE may occur as a consequence of the host response to infection, leading to deficits in cognition.
Publication Title
An integrated systems analysis implicates EGR1 downregulation in simian immunodeficiency virus encephalitis-induced neural dysfunction.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 124 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous. Several prognostic factors have been identified that can stratify patients into groups that differ in their relative tendency for disease progression and/or survival. Here, we pursued a subnetwork-based analysis of gene expression profiles to discriminate between groups of patients with disparate risks for CLL progression.
Publication Title
Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A (Tcf3) in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are premarked by the poised or active enhancer mark H3K4me1 in multipotent progenitors. Thus, in hematopoietic progenitors, multilineage priming of enhancer elements precedes commitment to the lymphoid or myeloid cell lineages.
Publication Title
Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are pre-marked by H3K4me1 in multipotent progenitors. However, H3K4me1 levels at a subset of enhancers are elevated during developmental progression, resulting in evolving enhancer repertoires that we propose orchestrate the myeloid and B cell fates.
Publication Title
Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The transcriptional data from an integrative analysis of transcriptional and metabolic stress responses that provides a more complete understanding of the mechanisms by which genetic regulatory circuits mediate metabolic phenotype.
Publication Title
Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina HiSeq 4000
Description
Single-cell analysis of KPC pancreatic tumor cells Overall design: Evaluate the single-cell transcriptomic landscape in 3 KPf/fC tumors
Publication Title
A Multiscale Map of the Stem Cell State in Pancreatic Adenocarcinoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- NextSeq 500
Description
mPDAC tumors of KPC mice Overall design: medium and large size tumors
Publication Title
A Multiscale Map of the Stem Cell State in Pancreatic Adenocarcinoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Soyfoods have been drawn the interrest in the roles that reducing risk of cardiovascular disease. Among various components, isoflavones have been come to the attention as beneficial soy ingredients. To evaluate the effectiveness of isoflavone content in dietary soybean (Glycine max) on modulating lipid metabolism, hepatic gene expressions involved in lipid metabolism were analyzed in rats. An isoflavone-rich cultivar (Yukipirika) and a conventional cultivar (Fukuyutaka) were employed. A principal component analysis (PCA) of microarray data was used to summarize characteristics of the experimental groups. As a result, the characteristics of the diets were largely explained by the first principal component (PC1). Soybean content in the diets distinctly separated in PC1. In contrast, isoflavone content had little effect on the mRNA expression.
Publication Title
Effects of soy protein and isoflavone on hepatic fatty acid synthesis and oxidation and mRNA expression of uncoupling proteins and peroxisome proliferator-activated receptor gamma in adipose tissues of rats.
Sample Metadata Fields
Age, Specimen part
View Samples