Filters
Technology
Platform
GSE59381
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
SOX2 is an oncogene and a core pluripotency transcription factor. SOX2 has multiple roles in various malignancies, in the maintainance of pluripotency and during various stages of embryonic development. Human embryonal carcinoma cells express SOX2 and the loss of this results in their differentiation.
Publication Title
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Schizosaccharomyces pombe
- 8 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Tristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a protein containing the critical features of the tristetraprolin zinc finger domain. zfs1 has been linked to pheromone signal transduction control and to the coordination of mitosis, but no biological function has been ascribed to the zfs1 protein. Through a functional genomics approach we compared transcript levels in wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1-deficient strain were examined for the presence of potential tristetraprolin-like binding sites. One such potential target transcript was encoded by arz1, a gene encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA decay was inhibited in the zfs1-deficient strain when it was expressed under the control of a thiamine-repressible promoter. Mutations within one AU-rich element present in the arz1 3-untranslated region protected this transcript from zfs1-promoted decay, whereas mutating another potential binding site had no effect. Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based probes; this interaction was eliminated when key residues were mutated in either zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model system for studies of zinc finger protein/AU-rich element interactions that result in mRNA decay.
Publication Title
Characterization of zfs1 as an mRNA-binding and -destabilizing protein in Schizosaccharomyces pombe.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient mice, and cells derived from them, showed that TTP could bind to certain AU-rich elements in mRNAs, leading to increases in the rates of mRNA deadenylation and destruction. Known physiological target
Publication Title
Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of stabilized transcripts in TTP-deficient fibroblasts.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Arsenic is a potent environmental toxin and a cause of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription. The influence of arsenic on post-transcriptional regulation, another important locus of gene expression control, has remained largely unexplored.
Publication Title
Global analysis of posttranscriptional gene expression in response to sodium arsenite.
Sample Metadata Fields
Cell line
View Samples- Schizosaccharomyces pombe
- 28 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins can bind directly to AU-rich elements in mRNAs and promote transcript deadenylation and decay. The yeast Schizosaccharomyces pombe expresses a single TTP family member, Zfs1p, that has been linked to the mating response pathway and septum formation. We showed previously that Zfs1p can bind to and promote the destabilization of AU-rich element-containing transcripts. In this study, we identified additional target transcripts by comparing transcript levels in wild type and zfs1 mutant yeast, using deep sequencing and microarray approaches. We also used direct RNA sequencing to determine the locations of the polyA tails in both wild type and mutant strains, and to confirm the presence of potential Zfs1p target sequences within the mRNA. These studies identified a set of transcripts containing potential Zfs1p binding sites that accumulated significantly in the zfs1 mutants; a subset of these turned over more slowly in the zfs1 mutant strain, and bound directly to Zfs1p in co-immunoprecipitations. One apparent direct target encodes the transcription factor Cbf12p, which is known to increase cell-cell adhesion and flocculation when over-expressed. Studies of zfs1 and cbf12 double mutants demonstrated that the increased flocculation seen in zfs1 mutants is due, at least in part, to a direct effect on the turnover of cbf12 mRNA, leading in turn to changes in the levels of its transcriptionally regulated genes. These data suggest that Zfs1p can both directly and indirectly regulate the levels of transcripts involved in cell-cell adhesion in this species.
Publication Title
Posttranscriptional regulation of cell-cell interaction protein-encoding transcripts by Zfs1p in Schizosaccharomyces pombe.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
The ZFP36L3 protein is a rodent-specific, placenta- and yolk sac-specific member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins. These proteins bind to AU-rich elements in target mRNAs, and promote their deadenylation and decay. Mice deficient in ZFP36L3 exhibited decreased neonatal survival rates, but no apparent morphological changes in the placenta or surviving offspring. Zfp36l3 is paternally imprinted, with profound parent-of-origin effects on gene expression. RNASeq of KO placental mRNA revealed many significantly affected transcripts, some of which exhibited decreased decay rates in differentiated trophoblast stem cells derived from KO blastocysts. The type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite an increase in its stability. This receptor is critical for placental iron uptake from the maternal circulation, and its decrease was accompanied by decreased iron stores in the KO fetus, suggesting that this intrauterine deficiency might have deleterious consequences in later life. Overall design: Examination of gene expression differences in yolk sac tissue between wild-type and knockout mice groups with 4 biological replicates in each group
Publication Title
Deficiency of the placenta- and yolk sac-specific tristetraprolin family member ZFP36L3 identifies likely mRNA targets and an unexpected link to placental iron metabolism.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 500
Description
Purpose: 1. Bulk-RNA-Seq was performed to identify tancytye-enriched genes. 2. scRNA-Seq was performed to profile hypothalamic cells following leptin treatment Conclusions: Leptin receptor expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms. Overall design: Methods 1 (Bulk-RNA-Seq). Flow-sorted RNA samples from Rax-EGFP BAC transgenic mice were sent to the Deep Sequencing and Microarray Core (Johns Hopkins University) for library preparation and sequencing. Briefly, polyadenylated RNA was purified from the total RNA samples using Oligo dT conjugated magnetic beads and prepared for single-end sequencing according to the Illumina TruSeq RNA Sample Preparation Kit v2 (# RS-122-2001, Illumina). The libraries were sequenced for paired-end 75 cycles using the TruSeq SBS kit on NextSeq 500 system. Filtered sequencing reads were mapped to the mouse reference genome (mm10) using TopHat. FPKM value for each gene was estimated using Cufflink. Methods 2 (scRNA-Seq). Mice brain coronal slices (aCSF- or leptin-infused) were dissociated using Act-Seq protocol and re-suspended cells were loaded into V2 10x Genomics Chromium Single Cell system, and libraries were sequenced on Illumina NextSeq with ~150 million reads per library. Sequencing results were processed 10x Genomics pipeline. Seurat V2 was used to perform downstream analysis following the standard pipeline using cells with more than 500 genes and 1000 UMI counts.
Publication Title
Tanycyte-Independent Control of Hypothalamic Leptin Signaling.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Global target mRNA specification and regulation by the RNA-binding protein ZFP36.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tristetraprolin/ZFP36/TTP and ELAVL1/HuR are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embyonic kidney cells and examined combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Among the targets ZFP36 binds and negatively regulates the mRNA of genes encoding proteins necessary for immune function and cancer, and other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance from ZFP36 overexpression independent of effects from confounding features, such as 3 UTR length. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes. ZFP36 preferentially interacts with and regulates AU-rich sequences while ELAVL1 prefers predominantly U- and CU-rich sequences. RNA target specificity identified by global in vivo ZFP36-mRNA interactions were quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 both bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to untangle the in vivo combinatorial regulation by RNA-binding proteins.
Publication Title
Global target mRNA specification and regulation by the RNA-binding protein ZFP36.
Sample Metadata Fields
Cell line, Treatment
View Samples