Similar Datasets
Project description:A chromosomal translocation fusion gene product EWS-WT1 is the defining genetic event in Desmoplastic Small Round Cell Tumor (DSRCT), a rare but aggressive tumor with a high rate of mortality. EWS-WT1 oncogene acts as an aberrant transcription factor that drives tumorigenesis, but the mechanism by which EWS-WT1 causes tumorigenesis is not well understood. To delineate the oncogenic mechanisms, we generated the EWS-WT1 fusion in the mouse using a gene targeting (knock-in) approach, enabling physiologic expression of EWS-WT1 under the native Ews promoter. We derived mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1. Remarkably, expression of EWS-WT1 led to a dramatic induction of many neuronal genes. Notably, a neural reprogramming factor, ASCL1 (achaete-scute complex-like 1), was highly induced by EWS-WT1 in MEFs and in primary DSRCT. Further analysis demonstrated that EWS-WT1 directly binds to the proximal promoter region of ASCL1 and activates its transcription through multiple WT1-responsive elements. Depletion of EWS-WT1 in a DSRCT cell line resulted in severe reduction in ASCL1 expression and cell viability. Remarkably, when stimulated with neuronal induction media, cells expressing EWS-WT1 expressed neural markers and generated neurite-like projections. These results demonstrate for the first time that EWS-WT1 activates neural gene expression and is capable of directing partial neuronal differentiation, likely via ASCL1. These findings suggest that stimulating DSRCT tumor cells with biological or chemical agents that promote neural differentiation might be a useful approach to develop novel therapeutics against this incurable disease. mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1 in 0 vs. 24 Hours in three replications (WT+KTS, or WT-KTS in 0, 24 H; CRE in 0 and 24H)
2014-09-11 | E-GEOD-53301 | biostudies-arrayexpress
Project description:We report the the identification of chrosomal regions bound by the Wilms' tumor suppressor gene WT1 during embryonic mouse kidney development. Two indepednent ChIP-Seq experiments on microdissected E18.5 developing mouse kidneys were carried out using either WT1-specific or IgG-antibodies as a negative control.
2014-06-15 | E-GEOD-58179 | biostudies-arrayexpress
Project description:We report the microRNA profiles of the mouse embryonic stem cell (E14IV), which have been deleted for tumour suppressor Wilms' Tumour 1 (WT1), and induced with retinoic acid. Additionally, cells that had an inducibe WT1 expression where also used to compare the microRNA profile during different time points of WT1 induction.
2024-03-26 | GSE169684 | GEO
Project description:We identified binding sites of the Wilms' tumor suppressor protein WT1 in the mouse podocyte genome in vivo by ChIP-seq. Furthermore, we provide a podocyte transcriptome derived from primary podocytes that were isolated by FACS on mouse glomeruli. In short, we show that WT1 activates a highly specific podocyte transcriptome by binding to putative podocyte-specific enhancers and TSS of target genes. Genes bound by WT1 in podocytes include the majority of genes mutated in hereditary podocytopathies as well as components of the slit diaphragm, actin cytoskeleton, extracellular matrix, and within endocytosis pathways. Furthermore, we infer a podocyte TF network from DNA-binding motifs enriched at WT1-bound loci that includes Tead, Lmx1b, Mafb, Tcf21, and Fox-class transcription factors.
2014-12-11 | GSE64063 | GEO
Project description:Background: Wilms' tumor gene 1 (WT1) acts as an oncogene in acute myeloid leukemia (AML). A naturally occurring alternative splice event between zinc fingers three and four, removing or retaining three amino acids (KTS), is believed to change the DNA binding affinity of WT1. Altered balance between WT1 -KTS and WT1 +KTS expression associates with poor prognosis in AML. Methods: We characterized the DNA binding patterns of biotin-tagged WT1 -KTS and WT1 +KTS in K562 cells by chromatin immunoprecipitation and deep sequencing (ChIP-seq). Results: We discovered that WT1 -KTS preferentially binds near transcription start sites (TSS) and in enhancers, whereas WT1 +KTS binds within gene bodies. Additionally, we observed a significant overlap between WT1 -KTS and WT1 +KTS target genes, despite the binding sites being distinct. Motif analysis showed enrichment of two TRANSFAC derived motif matrices within peaks for both isoforms, and enrichment of several previously published WT1 motifs which, however, differed between isoforms. Additional analyses showed that WT1 -KTS and WT1 +KTS target genes are transcribed to a higher extent than non-targets, and involved in cell proliferation, cell death, and development. Conclusions: Our results provide the first evidence that WT1 -KTS and WT1 +KTS bind principally different regions of the genome, yet share target genes. Our results indicate isoform-specific regulation of processes related to cell proliferation and differentiation, consistent with the involvement of WT1 in AML.
2016-12-24 | GSE81009 | GEO
Project description:A chromosomal translocation fusion gene product EWS-WT1 is the defining genetic event in Desmoplastic Small Round Cell Tumor (DSRCT), a rare but aggressive tumor with a high rate of mortality. EWS-WT1 oncogene acts as an aberrant transcription factor that drives tumorigenesis, but the mechanism by which EWS-WT1 causes tumorigenesis is not well understood. To delineate the oncogenic mechanisms, we generated the EWS-WT1 fusion in the mouse using a gene targeting (knock-in) approach, enabling physiologic expression of EWS-WT1 under the native Ews promoter. We derived mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1. Remarkably, expression of EWS-WT1 led to a dramatic induction of many neuronal genes. Notably, a neural reprogramming factor, ASCL1 (achaete-scute complex-like 1), was highly induced by EWS-WT1 in MEFs and in primary DSRCT. Further analysis demonstrated that EWS-WT1 directly binds to the proximal promoter region of ASCL1 and activates its transcription through multiple WT1-responsive elements. Depletion of EWS-WT1 in a DSRCT cell line resulted in severe reduction in ASCL1 expression and cell viability. Remarkably, when stimulated with neuronal induction media, cells expressing EWS-WT1 expressed neural markers and generated neurite-like projections. These results demonstrate for the first time that EWS-WT1 activates neural gene expression and is capable of directing partial neuronal differentiation, likely via ASCL1. These findings suggest that stimulating DSRCT tumor cells with biological or chemical agents that promote neural differentiation might be a useful approach to develop novel therapeutics against this incurable disease.
2014-09-11 | GSE53301 | GEO
Project description:We report the the identification of chrosomal regions bound by the Wilms' tumor suppressor gene WT1 during embryonic mouse kidney development.
2014-06-15 | GSE58179 | GEO
Project description:Interventions: A patient is vaccinated with Montanide ISA51-adjuvanted WT1 Trio cancer vaccine consisting of two WT1 CTL peptides (WT1-126 and WT1-235) and one WT1 HTL peptide (WT1-332) (2mg each) seven times at the interval of two weeks.
Primary outcome(s): Induction of WT1-specific immune responses assessed by WT1-related tests such as WT1-DTH skin reaction and serum levels of WT1 peptide IgG autoantibody at 1M, 2M, and 3M of WT1 Trio vaccine.
Study Design: Single arm Non-randomized
| 2638832 | ecrin-mdr-crc
Project description:We identified binding sites of the Wilms' tumor suppressor protein WT1 in the mouse podocyte genome in vivo by ChIP-seq. Furthermore, we provide a podocyte transcriptome derived from primary podocytes that were isolated by FACS on mouse glomeruli. In short, we show that WT1 activates a highly specific podocyte transcriptome by binding to putative podocyte-specific enhancers and TSS of target genes. Genes bound by WT1 in podocytes include the majority of genes mutated in hereditary podocytopathies as well as components of the slit diaphragm, actin cytoskeleton, extracellular matrix, and within endocytosis pathways. Furthermore, we infer a podocyte TF network from DNA-binding motifs enriched at WT1-bound loci that includes Tead, Lmx1b, Mafb, Tcf21, and Fox-class transcription factors. Examination of transcription factor binding sites for WT1 by ChIP-seq. Transcriptome analysis of podocytes by RNA-seq.
2014-12-11 | E-GEOD-64063 | biostudies-arrayexpress