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Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Disrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process.
Publication Title
ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.
Sample Metadata Fields
Specimen part, Treatment
View Samples
GSE50686- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Thousands of enhancers are characterized in the human genome, yet few have been shown important in cancer. Inhibiting oncokinases, such as EGFR, ALK, HER2, and BRAF, is a mainstay of current cancer therapy but is hindered by innate drug resistance mediated by upregulation of the HGF receptor, MET. The mechanisms mediating such genomic responses to targeted therapy are unknown. Here, we identify lineage-specific MET enhancers for multiple common tumor types, including a melanoma lineage-specific MET enhancer that displays inducible chromatin looping and MET gene induction upon BRAF inhibition. Epigenomic analysis demonstrated that the melanocyte-specific transcription factor, MITF, mediates this enhancer function. Targeted genomic deletion (<7bp) of the MITF motif within the MET enhancer suppressed inducible chromatin looping and innate drug resistance, while maintaining MITF-dependent, inhibitor-induced melanoma cell differentiation. Epigenomic analysis can thus guide functional disruption of regulatory DNA to decouple pro- and anti-oncogenic functions of tumor lineage-enriched transcription factors mediating innate resistance to oncokinase therapy.
Publication Title
Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Assay of gene expression pattern differences between liver cancer tissue and normal liver tissue from the same mouse by microarray in 4 separate mice injected with recombinant adeno-associated viral (AAV) vector
Publication Title
Assessing the potential for AAV vector genotoxicity in a murine model.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
IlluminaHiSeq2500
Description
We report a time course of RNA-seq data from wild-type embryonic stem cells and embryonic stem cells in which the cardiogenic transcription factors ZNF503, ZEB2 and NKX2-5 are depleted with shRNAs differentiating along the cardiac lineage. Overall design: Biological replicates of RNA-seq data from embryonic stem cells differentiating along the cardiac lineage.
Publication Title
An Orthologous Epigenetic Gene Expression Signature Derived from Differentiating Embryonic Stem Cells Identifies Regulators of Cardiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
To gain a deep understanding of mRNA turnover dynamics in mammalian cells, we pulse labeled newly synthesized RNA in 3t3 cells for 2 h with 4sU. RNA samples were fractionated into the newly synthesized and pre-existing fractions. Both fractions and the total RNA sample were analyzed by mRNA sequencing. We estimated mRNA half-lives based on the ratios of newly synthesized RNA/total RNA ratio and the preexisting RNA/total RNA.
Publication Title
Global quantification of mammalian gene expression control.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data prognostic biomarkers and novel therapeutic targets.
Publication Title
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sample Metadata Fields
Sex, Disease stage
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Cardiogenesis involves multiple biological processes acting in concert during development, a coordination achieved by the regulation of diverse cardiac genes by a finite set of transcription factors (TFs). Previous work from our laboratory identified the roles of two Forkhead TFs, Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu) in governing cardiac progenitor cell divisions by regulating Polo kinase activity. These TFs were also implicated in the regulation of numerous other cardiac genes. Here we show that these two Forkhead TFs play an additional and mutually redundant role in specifying the cardiac mesoderm (CM): eliminating the functions of both CHES-1-like and jumu in the same embryo results in defective hearts with missing hemisegments. Our observations indicate that this process is mediated by the Forkhead TFs regulating the fibroblast growth factor receptor Heartless (Htl) and the Wnt receptor Frizzled (Fz), both previously known to function in cardiac progenitor specification: CHES-1-like and jumu exhibit synergistic genetic interactions with htl and fz in CM specification, thereby implying function through the same genetic pathways, and transcriptionally activate the expression of both receptor-encoding genes. Furthermore, ectopic overexpression of either htl or fz in the mesoderm partially rescues the defective CM specification phenotype seen in embryos doubly homozygous for mutations in jumu and CHES-1-like. Together, these data emphasize the functional redundancy that leads to robustness in the cardiac progenitor specification process mediated by Forkhead TFs regulating the expression of signaling pathway receptors, and illustrate the pleiotropic functions of this class of TFs in different aspects of cardiogenesis.
Publication Title
Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
The development of a complex organ requires the specification of appropriate numbers of each of its constituent cell types, as well as their proper differentiation and correct positioning relative to each other. During Drosophila cardiogenesis, all three of these processes are controlled by jumeau (jumu) and Checkpoint suppressor homologue (CHES-1-like), two genes encoding forkhead transcription factors that we discovered utilizing an integrated genetic, genomic and computational strategy for identifying novel genes expressed in the developing Drosophila heart. Both jumu and CHES-1-like are required during asymmetric cell division for the derivation of two distinct cardiac cell types from their mutual precursor, and in symmetric cell divisions that produce yet a third type of heart cell. jumu and CHES-1-like control the division of cardiac progenitors by regulating the activity of Polo, a kinase involved in multiple steps of mitosis. This pathway demonstrates how transcription factors integrate diverse developmental processes during organogenesis.
Publication Title
Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
Sample Metadata Fields
Specimen part
View Samples