Genomics

Dataset Information

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Transcriptomic and Epigenomic Profiles of CIC-knockout and IDH1 mutant cells [histone_chip]


ABSTRACT: 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. Overall design: ChIP-seq against six histone marks performed in immortalized normal human astrocytes stably expressing IDH1-WT or IDH1-R132H, and in matched CIC knockout lines. Inputs were used as negative controls. Two independent replicates were obtained for each experiment.

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

ORGANISM(S): Homo Sapiens

SUBMITTER: Marco A Marra  

PROVIDER: GSE189857 | GEO | 2021-12-01

REPOSITORIES: GEO

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Publications

Integrative multi-omic analysis reveals neurodevelopmental gene dysregulation in CIC-knockout and IDH1-mutant cells.

Lee Stephen D SD   Song Jungeun J   LeBlanc Veronique G VG   Marra Marco A MA  

The Journal of pathology 20211222 3


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.  ...[more]

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