This SuperSeries is composed of the SubSeries listed below.
BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration.
Specimen part, Cell line
View SamplesMost cancer genomics papers to date have focused on aberrations in genomic DNA and protein-coding transcripts. However, around 50% of transcripts have no coding potential and may exist as non-coding RNA. We performed RNA-seq in BRAFv600e melanoma skin cancer and on melanocytes over-expressing oncogenic BRAF to catalog transcriptome remodeling. We discovered that BRAF regulates expression of 1027 protein coding transcripts, 39 annotated lncRNAs and 70 novel transcripts. Many of the novel transcripts are lncRNAs. We used an indepenedent dataset to interrogate our novel transcripts and found that the novel lncRNA BANCR is a BRAF-regulated lncRNA recurrently upregulated in melanoma. Knockdown of BANCR impairs melanoma cell migration.
BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration.
Cell line
View SamplesGene expression was measured from the dentate gyrus and entorhinal cortex harvested from human postmortem samples.
Molecular mechanism for age-related memory loss: the histone-binding protein RbAp48.
Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition.
Specimen part, Cell line, Treatment
View SamplesThousands 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.
Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition.
Cell line
View SamplesBackground: Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown.
1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1.
Specimen part, Cell line, Treatment, Time
View SamplesHuman cell line HCT116 incubated with Myxothiazol for 5 or 17 hours
A sustained deficiency of mitochondrial respiratory complex III induces an apoptotic cell death through the p53-mediated inhibition of pro-survival activities of the activating transcription factor 4.
No sample metadata fields
View SamplesGene expression profiling for identification of genes regulated by DNA methylation
Genome-wide screening of genes regulated by DNA methylation in colon cancer development.
Specimen part, Cell line
View SamplesActivation of b-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T-cells promotes thymocyte development without the requirement for preTCR signaling. We show here that activated b-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. b-Catenin induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional upregulation of c-Myc, whose activity is required for transformation since its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized b-catenin and remains low in the lymphomas indicating that Notch activation is not required or selected for in b-catenin induced lymphomas. Thus, b-catenin activation may provide a mechanism for the induction of T-ALL that does not depend on Notch activation.
Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation.
No sample metadata fields
View SamplesClassical embryological studies revealed that during mid-embryogenesis vertebrates show similar morphologies. This “phylotypic stage” has recently received support from transcriptome analyses, which have also detected similar stages in nematodes and arthropods. A conserved stage in these three phyla has led us to ask if all animals pass through a universal definitive stage as a consequence of ancestral constraints on animal development. Previous work has suggested that HOX genes may comprise such a ‘zootypic’ stage, however this hypothetical stage has hitherto resisted systematic analysis. We have examined the embryonic development of ten different animals each of a fundamentally different phylum, including a segmented worm, a flatworm, a roundworm, a water bear, a fruitfly, a sea urchin, a zebrafish, a sea anemone, a sponge, and a comb jelly. For each species, we collected the embryonic transcriptomes at ~100 different developmental stages and analyzed their gene expression profiles. We found dynamic gene expression across all of the species that is structured in a stage like manner. Strikingly, we found that animal embryology contains two dominant modules of zygotic expression in terms of their protein domain composition: one involving proliferation, and a second involving differentiation. The switch between these two modules involves induction of the zootype; which in addition to homeobox containing genes, also involves Wnt and Notch signaling as well as forkhead domain transcription factors. Our results provide a systematic characterization of animal universality and identify the points of embryological constraints and flexibility. Overall design: 139 single embryo samples.
The mid-developmental transition and the evolution of animal body plans.
Subject
View Samples