GSE180868 A temporal in vivo catalogue of chromatin accessibility and expression profiles in pineoblastoma reveals a prevalent role for repressor elements

Contributors : P Khoueiry ; R Saab ; S Idriss ; M Hallal ; A El-KurdiSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusPediatric pineoblastomas (PBs) are rare and aggressive tumors of grade IV histology. Although some oncogenic drivers are characterized, including germline mutations in RB1 and DICER1, the role of epigenetic deregulation and cis-regulatory regions in PB pathogenesis and progression is largely unknown. Here, we generated genome-wide gene expression, chromatin accessibility, and H3K27ac profiles covering key time-points of PB initiation and progression from pineal tissues of a mouse model of cyclin D1-driven pineoblastoma. We identified PB-specific enhancers and super-enhancers and found that, in some cases, the accessible genome dynamic precedes the transcriptome, a characteristic that is underexplored in tumor progression. During progression of PB, newly acquired open chromatin regions lacking H3K27ac signal become enriched for repressive state elements and harbor motifs of repressor transcription factors like HINFP, GLI2, and YY1. Copy number variant analysis identified deletion events specific to the tumorigenic stage, affecting among others the histone genes cluster and Gas1, the growth arrest specific gene. Gene set enrichment analysis and gene expression signatures positioned the model used here close to human PB samples demonstrating the potential...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research