STAT3 is a transcription factor playing a crucial role in inflammation, immunity and oncogenesis, able to induce distinct subsets of target genes in different cell types or under different conditions. Identification of direct transcriptional targets however has only defined a relatively limited set of genes, not sufficient to explain its variegated functions. In order to improve our understanding of the STAT3 transcriptional network we decided to develop a computational approach for the discovery of STAT3 functional binding sites. Upon generating a Positional Weight Matrix to define STAT3 binding sites, we applied a loglikelihood ratio scoring function and were able to assign affinity scores with very high specificity (93.5%) as measured by EMSA. STAT3 binding sites scoring above a stringent threshold have been identified genome-wide in Homo sapiens and Mus musculus and selected for phylogenetic conservation by genomic sequence alignment using eight vertebrate species. Validation was carried out on a subset of predicted
Genome-wide discovery of functional transcription factor binding sites by comparative genomics: the case of Stat3.
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Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells.
Specimen part, Cell line, Treatment, Time
View SamplesResults of blocking the HER-2 oncogene kinase function in SUM-225 cells by treatment with CP724,714 and measuring gene expression as a function of time provides information as to what genes are regulated by HER-2 in this breast cancer cell line.
Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells.
Specimen part, Cell line, Treatment, Time
View SamplesPurpose: The objective of this study was to determine cardiac transcriptional pathways regulated in response to 1.) hypothyroidism and re-establishment of a euthyroid state and 2.) Med13-dependent cardiac transcriptional pathways regulated in response to hypothyroidism and re-establishment of a euthyroid state Overall design: Methods: WT and Med13 cardiac-specific knockout mice (Med13cKO) were put on a normal chow or PTU diet at 8 weeks of age for a duration of 4 weeks. A third group was put on a PTU diet for 4 weeks followed by 3 daily injections of T3.
Regulation of cardiac transcription by thyroid hormone and Med13.
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View SamplesThe transcriptomic profiling of psoriasis has led to an increased understanding of disease pathogenesis. Although microarray technologies have been instrumental in this regard, it is clear that these tools detect an incomplete set of DEGs. RNA-seq can be used to supplement these prior technologies. Here, the use of RNAseq methods substantially increased the number of psoriasis-related DEGs. Furthermore, DEGs that were uniquely identified by RNA-seq, but not in other published microarray studies, further supported the role of IL-17 and tumor necrosis factor-a synergy in psoriasis. Examination of one of these factors at the protein level confirmed that RNA-seq is a powerful tool that can be used to identify molecular factors present in psoriasis lesions, and may be useful in the identification of therapeutic targets that to our knowledge have not been reported previously. Further studies are in progress to determine the biological significance of DEGs uniquely discovered by RNA-seq. Overall design: To define the transcriptomic profile of psoriatic skin, three pairs of lesional and nonlesional skin biopsy specimens were taken from patients with untreated moderate-to-severe plaque psoriasis.
Transcriptional profiling of psoriasis using RNA-seq reveals previously unidentified differentially expressed genes.
Specimen part, Subject
View SamplesCharacterization of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease. Here, we performed comprehensive gene expression profiling of cholangiocarcinoma tumors arising from bile duct inoculation of different grade malignant rat cholangiocytes.
Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas.
Sex
View SamplesThe increased -smooth muscle-actin positive cancer-associated fibroblastic cells (CAF) in the desmoplastic stroma may relate to a more aggressive cancer and worse survival outcomes for intrahepatic cholangiocarcinoma (ICC) patients
Novel organotypic culture model of cholangiocarcinoma progression.
Specimen part, Disease
View SamplesValidation of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease would provide an important resource for suggesting and testing of novel target-based therapies against this devastating cancer. In this study, comprehensive gene expression profiling in a novel orthotopic rat model of intrahepatic cholangiocarcinoma progression was carried out in an effort to identify potential therapeutic targets relevant to the progressive human cancer.
Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms.
Sex, Specimen part
View SamplesSnt2 is a yeast chromatin-interacting protein whose function has not been well characterized, that was recently shown to associate with Ecm5 and the Rpd3 deacetylase. Using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), we show that in response to H2O2, Snt2 and Ecm5 colocalize to promoters of genes involved in various aspects of the environmental stress response. By integrating these ChIP-seq results with expression analysis, we identify a key set of target genes that require Snt2 for proper expression after H2O2 stress. Finally, by mapping Snt2 and Ecm5 localization before and after rapamycin treatment, we identify a subset of H2O2-specific Snt2 and Ecm5 target promoters that are also targeted in response to rapamycin. Our results establish a function for Snt2 in regulating transcriptional changes in response to oxidative stress, and suggest Snt2 may have a role in additional stress pathways. Overall design: RNA-seq analysis to look at gene expression levels in wild-type, snt2 deletion, or ecm5 deletion strains before or 0.5 hours after treatment with H2O2 (final concentration 0.4 mM). This sequencing was done on biological triplicate samples.
The yeast Snt2 protein coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress.
Subject
View SamplesRNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish Overall design: Embryos derived from a zic2aGBT133/+; zic2bUW1127/+ incross were sorted by presence or absence of coloboma. RNA was prepared from each individual embryo at ~ 25 hpf
Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.
No sample metadata fields
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