Regulatory networks driving expression of genes critical for glioblastoma are controlled by the transcription factor c-Jun and the pre-existing epigenetic modifications

Glioblastoma (GBM, WHO grade IV) is an aggressive, primary brain tumor. Despite gross surgery and forceful radio- and chemotherapy, survival of GBM patients did not improve over decades. Several studies reported transcription deregulation in GBMs but regulatory mechanisms driving overexpression of GBM-specific genes remain largely unknown. Transcription in open chromatin regions is directed by transcription factors (TFs) that bind to specific motifs, recruit co-activators/repressors and a transcriptional machinery. Identification of GBM-related TFs-gene regulatory networks may reveal new, targetable mechanisms of gliomagenesis. Overall design: We predicted TFs-regulated networks in GBMs in silico and intersected them with putative TF binding sites identified in accessible chromatin in human glioma cells and GBMs. The Cancer Genome Atlas and gliomaAtlas datasets (DNA methylation, H3K27 acetylation, transcriptomic profiles) were explored to elucidate TFs-gene regulatory networks and effects of the epigenetic background