Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells [WGBS]
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ABSTRACT:
PROVIDER: PRJNA784800 | ENA |
REPOSITORIES: ENA
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Project description:Capicua (CIC)’s transcriptional repressor function is implicated in neurodevelopment and in oligodendroglioma (ODG) aetiology. However, CIC’s role in these contexts remains obscure, primarily from our currently limited knowledge regarding its biological functions. Moreover, CIC mutations in ODG invariably co-occur with a neomorphic IDH1/2 mutation, yet the functional relationship between these two genetic events is unknown. Here, we analysed models derived from an E6/E7/hTERT-immortalized (i.e. p53- and RB-deficient) normal human astrocyte cell line. To examine the consequences of CIC loss, we compared transcriptomic and epigenomic profiles between CIC wildtype and knockout cell lines, with and without mutant IDH1 expression. Our analyses revealed dysregulation of neurodevelopmental genes in association with CIC loss. CIC ChIP-seq was also performed to expand upon the currently limited ensemble of known CIC target genes. Among the newly identified direct CIC target genes were EPHA2 and ID1, whose functions are linked to neurodevelopment and the tumourigenicity of in vivo glioma tumour models. NFIA, a known mediator of gliogenesis, was discovered to be uniquely overexpressed in double mutant cells (CIC-knockout + IDH1-mutant). These results identify neurodevelopment and specific genes within this context as candidate targets through which CIC alterations may contribute to the progression of IDH-mutant gliomas.
2021-12-01 | GSE189860 | GEO
Project description:Capicua (CIC)’s transcriptional repressor function is implicated in neurodevelopment and in oligodendroglioma (ODG) aetiology. However, CIC’s role in these contexts remains obscure, primarily from our currently limited knowledge regarding its biological functions. Moreover, CIC mutations in ODG invariably co-occur with a neomorphic IDH1/2 mutation, yet the functional relationship between these two genetic events is unknown. Here, we analysed models derived from an E6/E7/hTERT-immortalized (i.e. p53- and RB-deficient) normal human astrocyte cell line. To examine the consequences of CIC loss, we compared transcriptomic and epigenomic profiles between CIC wildtype and knockout cell lines, with and without mutant IDH1 expression. Our analyses revealed dysregulation of neurodevelopmental genes in association with CIC loss. CIC ChIP-seq was also performed to expand upon the currently limited ensemble of known CIC target genes. Among the newly identified direct CIC target genes were EPHA2 and ID1, whose functions are linked to neurodevelopment and the tumourigenicity of in vivo glioma tumour models. NFIA, a known mediator of gliogenesis, was discovered to be uniquely overexpressed in double mutant cells (CIC-knockout + IDH1-mutant). These results identify neurodevelopment and specific genes within this context as candidate targets through which CIC alterations may contribute to the progression of IDH-mutant gliomas.
2021-12-01 | GSE189858 | GEO
Project description:Capicua (CIC)’s transcriptional repressor function is implicated in neurodevelopment and in oligodendroglioma (ODG) aetiology. However, CIC’s role in these contexts remains obscure, primarily from our currently limited knowledge regarding its biological functions. Moreover, CIC mutations in ODG invariably co-occur with a neomorphic IDH1/2 mutation, yet the functional relationship between these two genetic events is unknown. Here, we analysed models derived from an E6/E7/hTERT-immortalized (i.e. p53- and RB-deficient) normal human astrocyte cell line. To examine the consequences of CIC loss, we compared transcriptomic and epigenomic profiles between CIC wildtype and knockout cell lines, with and without mutant IDH1 expression. Our analyses revealed dysregulation of neurodevelopmental genes in association with CIC loss. CIC ChIP-seq was also performed to expand upon the currently limited ensemble of known CIC target genes. Among the newly identified direct CIC target genes were EPHA2 and ID1, whose functions are linked to neurodevelopment and the tumourigenicity of in vivo glioma tumour models. NFIA, a known mediator of gliogenesis, was discovered to be uniquely overexpressed in double mutant cells (CIC-knockout + IDH1-mutant). These results identify neurodevelopment and specific genes within this context as candidate targets through which CIC alterations may contribute to the progression of IDH-mutant gliomas.
2021-12-01 | GSE189857 | GEO
Project description:Capicua (CIC)’s transcriptional repressor function is implicated in neurodevelopment and in oligodendroglioma (ODG) aetiology. However, CIC’s role in these contexts remains obscure, primarily from our currently limited knowledge regarding its biological functions. Moreover, CIC mutations in ODG invariably co-occur with a neomorphic IDH1/2 mutation, yet the functional relationship between these two genetic events is unknown. Here, we analysed models derived from an E6/E7/hTERT-immortalized (i.e. p53- and RB-deficient) normal human astrocyte cell line. To examine the consequences of CIC loss, we compared transcriptomic and epigenomic profiles between CIC wildtype and knockout cell lines, with and without mutant IDH1 expression. Our analyses revealed dysregulation of neurodevelopmental genes in association with CIC loss. CIC ChIP-seq was also performed to expand upon the currently limited ensemble of known CIC target genes. Among the newly identified direct CIC target genes were EPHA2 and ID1, whose functions are linked to neurodevelopment and the tumourigenicity of in vivo glioma tumour models. NFIA, a known mediator of gliogenesis, was discovered to be uniquely overexpressed in double mutant cells (CIC-knockout + IDH1-mutant). These results identify neurodevelopment and specific genes within this context as candidate targets through which CIC alterations may contribute to the progression of IDH-mutant gliomas.
2021-12-01 | GSE189859 | GEO
Project description:Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells
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Project description:Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells [cic_chip]
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Project description:Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells [histone_chip]
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Project description:Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells [RNA-seq]
| PRJNA784801 | ENA
Project description:Type I low-grade gliomas (LGGs), characterized by 1p/19q co-deletions and IDH1/2 mutations, show superior overall survival compared to other gliomas. Approximately 70% of cases harbour mutations in the Capicua (CIC) gene, whose product is a transcriptional repressor whose transcriptional network has yet to be extensively studied in human cells. To address this, we developed CIC knockout cell lines and used transcriptome analyses to study the consequences of CIC loss. Results were further compared to data for Type I LGGs and stomach adenocarcinomas from The Cancer Genome Atlas (TCGA). We find that CIC appears to regulate the expression of genes involved in cell-cell adhesion and nervous system development. CIC deficiency is also found to be associated with a MEK activation transcriptional signature and to act as an effector of MEK signalling. Loss of CIC may thus present a novel mechanism for the dysregulation of this and other oncogenic pathways.
2017-04-15 | GSE80359 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-11-30 | GSE189861 | GEO