2021
DOI: 10.1002/path.5835
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Integrative multi‐omic analysis reveals neurodevelopmental gene dysregulation in CIC‐knockout and IDH1‐mutant cells

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-defi… Show more

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Cited by 7 publications
(10 citation statements)
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“…Binding of CIC to gene loci recruits histone deacetylases leading to transcriptional repression underpinning CIC function in development and tumorigenesis [ 63 ]. Targets of CIC regulation commonly identified in mammalian transcriptomic studies are the PEA3 sub-family of ETS transcription factors and DUSP Mapk phosphatases [ 40 , 64 66 ]. Interestingly, our transcriptomic analyses show that early expression of these genes does not significantly change in Cic knockdown embryos.…”
Section: Discussionmentioning
confidence: 99%
“…Binding of CIC to gene loci recruits histone deacetylases leading to transcriptional repression underpinning CIC function in development and tumorigenesis [ 63 ]. Targets of CIC regulation commonly identified in mammalian transcriptomic studies are the PEA3 sub-family of ETS transcription factors and DUSP Mapk phosphatases [ 40 , 64 66 ]. Interestingly, our transcriptomic analyses show that early expression of these genes does not significantly change in Cic knockdown embryos.…”
Section: Discussionmentioning
confidence: 99%
“…The 325 cohort and 693 cohort from the Chinese Glioma Genome Atlas (CGGA, http://www.cgga.org.cn/) were utilized for the validation of treatment response. Additionally, for validation purposes, we acquired data from 24 samples, including RNA-seq, DNA methylation-seq, and ChIP-seq, from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/, GEO accession: GSE121719, GSE121720, GSE121721, GSE189859, GSE189860, and GSE189857) 20,21 . Data for chromosomal three-dimensional structures (TADs) was retrieved from GSE77565 22 .…”
Section: Data Collection and Quality Controlmentioning
confidence: 99%
“…CIC ChIP-seq peaks for NHA cells were obtained from Lee et al [24] (Table S3 in that publication). ChIP-seq data from mouse embryonic stem cells (mESCs; fastq files) were downloaded from ArrayExpress (ERR2534130 [CIC ChIP] and ERR2534131 [IgG control], data from Weissmann et al [22]) and SRA (SRR7643337…”
Section: Chip-seq Analysismentioning
confidence: 99%
“…CIC is a transducer of receptor tyrosine kinase (RTK) signalling and functions through a default repression mechanism in which RTK activation leads to reduced CIC activity and subsequent de-repression of its target genes [19]. Targets of CIC are also themselves enriched for genes involved in the mitogen-activated protein kinase (MAPK) signalling cascade, including effectors (e.g., PTPN9, SHC3/4) and members of regulatory feedback mechanisms (e.g., DUSP4/5/6, SPRY2/4, SPRED1/2/3) [13,[20][21][22][23][24]. The cancer-promoting properties observed in cells with disrupted CIC activity have been explained, at least in part, by the de-repression of one or more of its known target genes that are effectors of MAPK signalling, especially the ETS transcription factors ETV1, ETV4, and ETV5 [8][9][10].…”
Section: Introductionmentioning
confidence: 99%