CIC and ATXN1L knockout gene expression data [NHA]
Ontology highlight
ABSTRACT: CIC has recently been implicated as a negative prognostic factor in multiple cancers. CIC and ATXN1L have been reported as interactors in several cellular contexts including development and disease state. To investigate the relationship between CIC and ATXN1L on a transcriptomic level, CIC-KO and ATXN1L-KO cell lines were generated. Gene expression profiling of CIC-KO and ATXN1L-KO cell lines was performed by microarray and differentially expressed genes were compared. We found a high degree of overlap in differentially expressed genes in CIC-KO and ATXN1L-KO suggesting loss of either interacting partner to lead to similar transcriptomic changes.
Project description:CIC has recently been implicated as a negative prognostic factor in multiple cancers. CIC and ATXN1L have been reported as interactors in several cellular contexts including development and disease state. To investigate the relationship between CIC and ATXN1L on a transcriptomic level, CIC-KO and ATXN1L-KO cell lines were generated. Gene expression profiling of CIC-KO and ATXN1L-KO cell lines was performed by microarray and differentially expressed genes were compared. We found a high degree of overlap in differentially expressed genes in CIC-KO and ATXN1L-KO suggesting loss of either interacting partner to lead to similar transcriptomic changes.
Project description:Aberrations in Capicua (CIC) have recently been implicated as a negative prognostic factor in a multitude of cancer types through activation of the MAPK signalling cascade and derepression of oncogenic ETS transcription factors. The Ataxin-family protein ATXN1L has previously been reported to interact with CIC in developmental and disease contexts to facilitate the repression of CIC target genes. To further investigate this relationship, we performed functional in vitro studies utilizing ATXN1LKO and CICKO human cell lines and characterized a reciprocal functional relationship between CIC and ATXN1L.
Project description:Although expansion of a polyglutamine tract in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of wild-type ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To gain insight into the function of these proteins, we generated and characterized Atxn1L-/- and Atxn1-/- ; Atxn1L-/- double mutant animals. We found that Atxn1L -/- mice have several developmental problems including hydrocephalus, omphalocoele and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1-/- ; Atxn1L-/- mice, suggesting that Atxn1 and Atxn1L are functionally redundant. To unravel the molecular mechanism underlying the alveolarization defect in Atxn1-/- mice, we carried out microarray analyses using total lung RNA from WT, Atxn1-/- and Atxn1L-/- mice Lung tissues were dissected from 6 day old mice from either Atxn1 heterozyous intercrosses or Atxn1L heterozygous intercrosses. We collected lung tissue samples from 4 pairs of WT and Atxn1-/- amd 3 pairs of WT and Atxn1-/- mice. Total RNA extracted from the samples was subjected to microarray analysis using Affymetrix mouse gene ST 1.0 array. GSM731591-GSM731598 (Atxn1L KO and controls) and GSM731599-GSM731604 (Atxn1 KO and controls) were RMA-processed separately.
Project description:We compared gene expression differences in Atxn1L knockout vs wildtype HSCs KO allele described in Pub Med ID: 22014525 HSCs were purified as Lineage-negative, Sca-1+ c-Kit+ (LSK), CD150+ and Side population from both Atxn1L-null and WT mice on C57Bl/6 background
Project description:Although expansion of a polyglutamine tract in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of wild-type ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To gain insight into the function of these proteins, we generated and characterized Atxn1L-/- and Atxn1-/- ; Atxn1L-/- double mutant animals. We found that Atxn1L -/- mice have several developmental problems including hydrocephalus, omphalocoele and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1-/- ; Atxn1L-/- mice, suggesting that Atxn1 and Atxn1L are functionally redundant. To unravel the molecular mechanism underlying the alveolarization defect in Atxn1-/- mice, we carried out microarray analyses using total lung RNA from WT, Atxn1-/- and Atxn1L-/- mice
Project description:CIC encodes a transcriptional repressor inactivated by loss-of-function mutations in several cancer types, indicating that it may function as a tumor suppressor. Recent data indicate that CIC may regulate cell cycle genes in humans; however, a thorough investigation of this proposed role has not yet been reported. Here, we used single-cell RNA sequencing technology to provide evidence that inactivation of CIC in human cell lines resulted in transcriptional dysregulation of genes involved in cell cycle control. We also mapped CIC’s protein-protein and genetic interaction networks, identifying interactions between CIC and members of the Switch/Sucrose Non-Fermenting (SWI/SNF) complex, as well as novel candidate interactions between CIC and cell cycle regulators. We further showed that CIC loss was associated with an increased frequency of mitotic defects in human cell lines and a mouse model. Overall, our study positions CIC as a cell cycle regulator and indicates that CIC loss can lead to mitotic errors, consistent with CIC’s emerging role as a tumor suppressor of relevance in several cancer contexts.
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.