CANONICAL HISTONE H3 VARIANTS ARE LINKED TO CELL CYCLING IN GLIOBLASTOMA

Glioblastomas (GBM) are the most prevalent primary tumours in the central nervous system, which are characterized by a special aggressivity and poor outcome that is difficult to tackle due to their high heterogeneity across patients. Epigenetic dysregulation is of paramount importance to maintain the proliferative and self-perpetuation properties of tumoural cells and can be reversed by pharmacological means. In this work, we have examined the expression and function of the main histone H3 variants (the canonical H3.1/H3.2 and the alternative H3.3) across diverse types of gliomas and glioneural tumours with particular emphasis in GBM. To this aim, we used our in-house multiomics datasets from FFPE-derived tumours and we manipulated GBM cultures derived from patients. As a result, we determined that a high expression of canonical H3 variants was generally associated with brain tumours of high aggressiveness and lower survival, and correlated with the induction of genes related to mitosis and nucleosome assembly. Blocking the cell cycle in cultured cells dramatically lowered the expression of H3-1/H3.2 genes and, conversely, interfering H3.1 transcripts reduced cell viability. Contrary to expectations, the replication-independent H3.3 has not simply counteracting activities. The study presented here opens the possibility for canonical histone variants as biomarkers of therapeutically targetable cells.