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GSE22610
Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The nuclear receptor, estrogen receptor alpha (ER), controls the expression of hundreds of genes responsible for target cell phenotypic properties, but the relative importance of direct vs. tethering mechanisms of DNA binding has not been established. In this first report, we examine the genome-wide chromatin localization of an altered-specificity mutant ER with a DNA-binding domain deficient in binding to estrogen response element (ERE)-containing DNA (DBDmut ER) vs. wild type ER. Using high-throughput sequencing of ER chromatin immunoprecipitations (ChIP-Seq) and mRNA transcriptional profiling, we show that direct ERE binding is required for most (75%) estrogen-dependent gene regulation and 90% of hormone-dependent recruitment of ER to genomic binding sites. De novo motif analysis of the chromatin binding regions in MDA-MB-231 human breast cancer cells defined unique transcription factor profiles responsible for genes regulated through tethering vs. direct DNA (ERE) binding, with Runx motifs enriched in ER-tethered sites. We confirmed a role for Runx1 in mediating ERa genomic recruitment and regulation of tethering genes. Our findings delineate the contributions of ERE binding vs. binding through response elements for other transcription factors in chromatin localization and ER-dependent gene regulation, paradigms likely to underlie the gene regulatory actions of other nuclear receptors as well.
Publication Title
Genome-wide analysis of estrogen receptor alpha DNA binding and tethering mechanisms identifies Runx1 as a novel tethering factor in receptor-mediated transcriptional activation.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Estradiol Timecourse of MDA-MB-231ER+ cells containing a WT-ER and DBDmut-ER
Publication Title
Genome-wide analysis of estrogen receptor alpha DNA binding and tethering mechanisms identifies Runx1 as a novel tethering factor in receptor-mediated transcriptional activation.
Sample Metadata Fields
Time
View Samples- Mus musculus, Homo sapiens
- 71 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
In this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Publication Title
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseRef-8 v2.0 expression beadchip
Description
In this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Publication Title
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies.
Publication Title
Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy.
Sample Metadata Fields
Sex, Age, Disease, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
iPSC were obtained from DPC from TRPC6-mut patient, a idiopathic autistic patient and a control. Original DPC and iPSC obtained were submited to expression analysis in order to check if the expression pattern obtained for the iPSC cells were closer related to embyonic cells than to the original DPC
Publication Title
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Trophoblast is the primary epithelial cell type in the placenta, a transient organ required for proper fetal growth and development. We have identified a CDX2+/p63+ cytotrophoblast (CTB) subpopulation in the early post-implantation human placenta, which is significantly reduced later in gestation. CTB differentiate into different trophoblast subtypes, which are responsible for gas/nutrient exchange (syncytiotrophoblast/STB) and invasion and maternal vascular remodeling (extravillous trophoblast/EVT). Study of early human placental development is severely hampered by lack of a representative trophoblast stem cell (TSC) model, with the capacity for self-renewal and the ability to differentiate into both STB and EVT. We describe a reproducible protocol, using defined media containing BMP4, by which human embryonic stem cells (hESC) can be differentiated into CDX2+/p63+ CTB-like cells. These cells can be replated to further differentiate into STB- and EVT-like cells, based on marker expression, hormone secretion and invasive ability. Differentiation of hPSC-derived CTB in hypoxia leads to reduced hCG secretion and STB-associated gene expression, instead inducing EVT differentiation in a hypoxia-inducible factor-dependent manner.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
In this study we identified that Sirt1 is important for mouse trophoblast stem cell (TSC) differentiation. The transcriptome of wild-type and Sirt1-null TSC were analyzed to identify dysregulation of signaling pathways.
Publication Title
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Sample Metadata Fields
No sample metadata fields
View Samples