Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma‐initiating cells

Glioblastoma ( GBM ) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG 1 and TLE 1 promote GBM propagation by supporting maintenance of brain tumour‐initiating cells (BTICs) with stem‐like properties. Here, we characterize FOXG 1 and TLE 1 target genes in GBM patient‐derived BTICs using Ch IP ‐Seq and RNA ‐Seq approaches. These studies identify 150 direct FOXG 1 targets, several of which are also TLE 1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis. Negative regulators of NOTCH signalling, including CHAC 1 , are among the transcriptional repression targets of FOXG 1: TLE 1 complexes, suggesting a crosstalk between FOXG 1: TLE 1 and NOTCH ‐mediated pathways in GBM . These results provide previously unavailable insight into the transcriptional programs underlying the tumour‐promoting functions of FOXG 1: TLE 1 in GBM .