PO-399 Genome wide histone modification patterns at the promoter regions are distinct in low and high grade gliomas

Introduction Growing evidence indicates global dysregulation of epigenetics in gliomas as a driving force of transcriptional changes and pathogenic mechanisms. Gliomas, the most common primary brain tumours, are clinically divided by WHO into 4 grades according to their malignancy. Slowly growing, pilocytic astrocytomas (PA, grade I) are the benign and most treatable of the gliomas, with a cure rate of over 90 percent. Glioblastomas (GBM, grade IV) are aggressive tumours with poor prognosis due to diffusive nature and resistance to current therapies. We endeavoured to provide a global view of epigenetic landscape of regulatory regions in combination with transcriptomes to identify gene regulatory networks that may contribute to tumorigenesis and tumour malignancy. Material and methods To achieve these goals, we collected glioma samples obtained as fresh surgical resections, produced single cell suspension and on each tumour sample we performed multilayer genome-wide analyses to identify open chromatin areas (Assay for Transposase-Accessible Chromatin using sequencing, ATAC-seq) and histone modification patterns (Chromatin immunoprecipitation, ChIP-seq) in combination with transcriptome analyses (RNA-seq). Besides annotation of functional regulatory sites in tumours, we performed comparative analyses of glioma of different grades to identify dysregulations associated with tumour malignancy. Results and discussions We found that the global distribution of H3K4me3 ChIPseq peaks indicates that different glioma grades share similar genome-wide pattern of H3K4me3 enrichment in regions surrounding a transcription start site (TSS). However, we found a striking shift in enrichment levels of active histone marks around TSS from H3K4me3 towards H3K27ac in GBM. Conclusion In conclusion, this study is the very first identification of open chromatin and epigenetic regulatory networks in low and high grade gliomas. Our results demonstrate distortion of histone active marks in GBM and suggest that H3K27ac plays more important role in glioma malignancy then H3K4me3. Supported by SYMFONIA 2015/16/W/NZ2/00314 grant from the National Science Centre, Poland