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Figure 1. Illustration of the different epigenetic modifications that target chromatin and contribute to treatment resistance in GBM. (A) DNA methylation silences the promoters of tumor suppressor genes, hence contributing to the proliferative ability of GBM cells. This mechanism also has the ability to suppress the expression of inhibitors of the WNT pathway (WIF1, DKKF, NKD, sFRP) and RAS pathway (RASSF1A); (B) Histone acetylation, which is achieved by histone acetylases and reversed by histone deacetylases, can also contribute to the regulation of chromatin structure and gene expression. For example, histone acetylation by KAT6A can lead to increased expression of the genes involved in the overactivation of the PI3K/AKT oncogenic pathway. This is reversed by the histone deacetylase HDAC1; (C) Histone methylation is another alteration that can control the expression of genes. For instance, the interplay between the histone methylase MLL and the demethylase KDM1 can regulate the expression of HOX genes, which are implicated in cancer proliferation and treatment resistance; (D) The chromatin remodeling complex SWI/SNF can alter the architecture of chromatin through several of its domains. One such domain, ACTL6A, can promote the expression of the YAP/TAZ pathway, which, in turn, contributes to treatment resistance. GBM: Glioblastoma multiforme; MGMT: methylguanine methyltransferase; PTEN: phosphatase and tensin homolog; WNT: wingless; WIF: WNT inhibitory factor; DKKF: dickkopf; NKD: naked cuticle; sFRP: secreted frizzled-related protein family; RASSF1: ras association domain family; HDAC: histone deacetylase; KAT: lysine acyltransferase; MLL: mixed lineage leukemia; KDM: histone lysine demethylase; SWI/SNF: switch/sucrose non-fermentable; ACTL6A: actin-like protein 6A; PI3K/AKT: phosphoinositide-3-kinase-protein kinase B; HOX: homeobox; YAP/TAZ: yes-associated protein/transcriptional co-activator with PDZ-binding motif.