Elucidation of the BMI1 interactome identifies novel regulatory roles in glioblastoma

Glioblastoma (GBM) is the most common and aggressive intrinsic brain tumour in adults. Epigenetic mechanisms controlling normal brain development are often dysregulated in GBM. Among these, BMI1, a structural component of the Polycomb Repressive Complex 1 (PRC1), which promotes the H2AK119ub catalytic activity of Ring1B, is upregulated in GBM and its tumorigenic role has been shown in vitro and in vivo. Here, we have used protein and chromatin immunoprecipitation followed bymass spectrometry (MS) analysis to elucidate the protein composition of PRC1 in GBM and transcriptional silencing of defining interactors in primary patient-derived GIC lines to assess their functional impact on GBM biology. We identify novel regulatory functions in mRNA splicing and cholesterol transport which could represent novel targetable mechanisms in GBM.

Automated summary

Glioblastoma (GBM) is a common and aggressive brain tumor in adults, with dysregulated epigenetic mechanisms. BMI1, a component of PRC1, is upregulated in GBM and has been shown to play a tumorigenic role. Research has identified new regulatory functions of PRC1 in mRNA splicing and cholesterol transport in GBM, potentially offering novel targetable mechanisms for treatment.