Genomics

Dataset Information

40

Integrative epigenomic and Master Regulator analysis of adult glioblastoma - cell line RNAseq experiments


ABSTRACT: Cancer Master Regulators (MRs) are proteins that define the cancer cell state via transcriptional regulation. An unexplored aspect of cancer MRs is how changes in their activity affect epigenetics. Adult glioblastoma (GB) consists of four methylation subtypes. However, the epigenetic landscapes and gene regulatory networks (GRNs) of each remains uncharacterised. We present an integrated epigenomic characterisation and MR identification of GB subtypes using a cohort of 60 deeply characterised adult GBs. We identify SOX10 as a RTK I subtype MR, whose loss causes a MES subtype transition. We describe differences between subtypes in their methylation and chromatin landscapes at base-pair resolution, including a novel CpG Island Methylator Phenotype (CIMP)-like pattern of hypermethylation targeting normal brain (NBr) bivalent promoters in the RTK II subtype. We identified 10 consensus MRs using orthogonal analyses of superenhancers and gene co-expression networks, and we show that the loss of SOX10 in an RTK I model results in MR activation and phenotypic and epigenetic changes characteristic of the MES subtype. Our analysis is the first comprehensive comparative analysis of GB subtype epigenomes, and illustrates the interplay between epigenetics, gene expression, MR activity and cellular phenotypes. We also make our data available to the community via a publically-accessible genome browser. Overall design: The RTK I-like glioblastoma cell line model LN229 was transduced with CRISPRi and sgRNAs repressing expression of the SOX10 gene. RNAseq was performed in the control and SOX10 knockdown conditions. Please note that the processed data files generated from multiple samples are linked as Series supplementary files [2] Raw data requires controlled access and is deposited at EGAS00001003230.

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Bernhard Radlwimmer  

PROVIDER: GSE121717 | GEO | 2018-11-05

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
GSE121717_ExpressionArray_shSOX10_LN229_CRISPRi_limma_results_table.txt.gz Txt
GSE121717_RAW.tar Raw
filelist.txt Txt
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