TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [ChIP-seq]

We investigated the contribution of TOP2B to transcriptional modulation in gliomas given the variable expression of this helicase across tumors, and its emerging role in epigenetic regulation of transcription. We mapped the genomic location of TOP2B, and identified distinct sites of native binding and enzymatic activity across human glioma cell lines and human tumor specimens. TOP2B was active in a subset of promoters and introns, and its inhibition led to downregulation of these genes. We investigated the contribution of TOP2B to transcriptional modulation in gliomas given the variable expression of this helicase across tumors, and its emerging role in epigenetic regulation of transcription. We mapped the genomic location of TOP2B, and identified distinct sites of native binding and enzymatic activity across human glioma cell lines and human tumor specimens. TOP2B was active in a subset of promoters and introns, and its inhibition led to downregulation of these genes. Overall design: We performed ChIP-seq (Chromatin immunoprecipitation and sequencing) for TOP2A and TOP2B to investigate its genomic localization in proneural glioma genotypes TS543 and BT142 and two mesenchymal glioma cell lines SNB19 and 0777A. To analyze the contribution of TOP2B on gene expression we treated cells with the TOP2 inhibitor ICRF193 10Um for 5hrs followed by RNA-seq. 20 TS543 samples (10 untreated; 10 treated), 12 BT142 samples (5 untreated; 7 treated) were included in the study.