Genome wide WT1 binding sites in developing mouse kidneys
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE58179 | GEO | 2014/06/15
SECONDARY ACCESSION(S): PRJNA251516
REPOSITORIES: GEO
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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:The Wilms tumor 1 (WT1) gene encodes a zinc finger transcription factor important for normal kidney development. WT1 is a suppressor for Wilms tumor development and an oncogene for diverse malignant tumors. We recently established cell lines from primary Wilms tumors and identified the corresponding WT1 mutations (see GSE18058). To investigate the function of mutant WT1 proteins we performed WT1 knockdown experiments in primary Wilms tumor cell lines with a frameshift/extension (p.V432fsX87 = Wilms3) and a stop mutation (p.P362X = Wilms2) of WT1, followed by genome wide gene expression analysis. A detailed analysis of these gene expression data using MetaCore enabled us to classify the WT1 mutations as gain of function mutations. The mutant WT1Wilms2 and WT1Wilms3 proteins acquired an ability to modulate the expression of a highly significant number of genes from the G2/M phase of the cell cycle, and WT1 knockdown experiments showed that they are required for Wilms tumor cell proliferation. Data from the literature show that p53 negatively regulates the activity of a large number of these genes which are also part of a core proliferation cluster in diverse human cancers. Our data strongly suggest that mutant WT1 proteins facilitate expression of these cell cycle genes by antagonizing transcriptional repression mediated by p53. In light of this it is important to note that mutant WT1 has an ability to physically interact with the tumor suppressor p53. Together the findings show for the first time, that mutant WT1 proteins have a gain of function and act as oncogenes for Wilms tumor development by regulating Wilms tumor cell proliferation. siWT1 mediated knockdown in two Wilms tumor cell lines one and two days after transfection versus non-silencing controls
2014-05-12 | E-GEOD-54635 | biostudies-arrayexpress
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
Project description:The Wilms tumor 1 (WT1) gene encodes a zinc finger transcription factor important for normal kidney development. WT1 is a suppressor for Wilms tumor development and an oncogene for diverse malignant tumors. We recently established cell lines from primary Wilms tumors and identified the corresponding WT1 mutations (see GSE18058). To investigate the function of mutant WT1 proteins we performed WT1 knockdown experiments in primary Wilms tumor cell lines with a frameshift/extension (p.V432fsX87 = Wilms3) and a stop mutation (p.P362X = Wilms2) of WT1, followed by genome wide gene expression analysis. A detailed analysis of these gene expression data using MetaCore enabled us to classify the WT1 mutations as gain of function mutations. The mutant WT1Wilms2 and WT1Wilms3 proteins acquired an ability to modulate the expression of a highly significant number of genes from the G2/M phase of the cell cycle, and WT1 knockdown experiments showed that they are required for Wilms tumor cell proliferation. Data from the literature show that p53 negatively regulates the activity of a large number of these genes which are also part of a core proliferation cluster in diverse human cancers. Our data strongly suggest that mutant WT1 proteins facilitate expression of these cell cycle genes by antagonizing transcriptional repression mediated by p53. In light of this it is important to note that mutant WT1 has an ability to physically interact with the tumor suppressor p53. Together the findings show for the first time, that mutant WT1 proteins have a gain of function and act as oncogenes for Wilms tumor development by regulating Wilms tumor cell proliferation.
2014-05-12 | GSE54635 | GEO
Project description:The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that plays important roles during development of several organs including metanephric kidneys. A number of WT1 target genes have been identified, but the detailed mechanisms by which WT1 orchestrates renal development remain elusive. To identify WT1 target genes relevant to development, genome-wide expression profiling was performed using oligonucleotide microarrays representing 39,000 human transcripts Keywords: Wilms' tumor 1 (WT1) gene, -KTS isoform; time course
2007-06-21 | GSE5117 | GEO
Project description:LB-22 is an immortalized mesenchymal cell line derived from embryonic kidneys of 'immortomice'. Immortomice ubiquitously express an interferon-inducible, temperature-sensitive SV-40 large T antigen. LB-22 cells were selected for endogenous abundant expression of the mouse Wilms' tumor suppressor homolog WT1, an important transcription factor in kidney development. Here, we assessed changes in gene expression in response to siRNA mediated WT1 knockdown.
2015-02-28 | GSE66356 | 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:LB-22 is an immortalized mesenchymal cell line derived from embryonic kidneys of 'immortomice'. Immortomice ubiquitously express an interferon-inducible, temperature-sensitive SV-40 large T antigen. LB-22 cells were selected for endogenous abundant expression of the mouse Wilms' tumor suppressor homolog WT1, an important transcription factor in kidney development. Here, we assessed changes in gene expression in response to siRNA mediated WT1 knockdown. LB-22 cells were transfected either with WT1 siRNA or scramble Control siRNA. Total RNA was extracted 48 hours after transfection and Affymetrix Mouse 430.2 expression arrays were hybridized according to standard protocols. CEL files not available for this dataset.
2015-02-28 | E-GEOD-66356 | biostudies-arrayexpress
Project description:Here we identify -KTS, a major alternatively spliced isoform of the Wilms’ tumor suppressor WT1, as a key determinant of female sex determination.
2024-02-13 | GSE207097 | GEO
Project description:Absence of WT1 during kidney organoid development from human induced pluripotent stem cells (iPSCs) induces hallmarks of Wilms tumorigenesis. To define underlying transcriptional alterations and similarities to human patients, we performed timecourse RNA-seq of kidney organoid development from control iPSCs (control, not edited) and in the absence of WT1. Two timepoints for knockout (KO) of WT1 were investigated: In iPSCs (KO in iPSCs), and between day 4 and day 7 of organoid formation (KO d4-7).
2021-08-01 | E-MTAB-9957 | biostudies-arrayexpress