Table 2 Dysregulation of gene transcription resulting from the activity of chromatin regulators in adult and pediatric high-grade gliomas. Epigenetic dysregulation arises from changes in histone acetylation and methylation through changes in protein expression and activity to affect gene transcription. BET – bromodomain and extraterminal; EZH2 – enhancer of zeste homolog 2; HDAC – histone deacetylase; H3K4/9/27 – histone 3 lysine 4/9/27; LSD1 – lysine-specific demethylase 1; PRMT – protein arginine methyltransferase (PRMT) family
Epigenetic modification | Protein(s) | Function | Effect on gene transcription | Implications in HGG |
|---|---|---|---|---|
Histone acetylation | HDAC family | Acetyl eraser | Remove acetyl groups at H3K4 to downregulate gene expression | Overexpression of HDAC 1/2/3/7 [26] |
| Â | BET family | Acetyl reader | Recognize acetylated lysine residues to activate or repress transcription | Overexpression of BRD2 and BRD4 [27] |
Histone methylation | PRMT family | Methyl writer | Dual activity as a transcriptional activator and repressor depending on histone mark subject to arginine methylation | PRMT 1/2/5/3/6 upregulated or overexpressed in HGG [28,29,30,31, 51, 52] |
EZH2 | Methyl writer | Transcriptional repression via hypermethylation of histone H3K27 | Overexpression in gliomas is associated with poor prognosis [32, 33] | |
LSD1 | Methyl eraser | Demethylate lysine residues on H3K4 to repress gene transcription and on H3K9 to activate gene transcription |