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. 2017 May 17;8(5):145. doi: 10.3390/genes8050145

Table 2.

Evidence of epigenetic mechanisms effecting ALT in human or mouse.

EM 1 Effect 2 Modifier Target Mode of Action References
DNA − Dnmt1, Dnmt3a/b 4 Subtelomere Methylation [19]
− TA, Tr 4 Subtelomere Methylation [127]
− Rbl2-dependent Dnmt3a/b 4 Subtelomere Methylation [128]
− Tet CpG Demethylation [129]
+ ? CpG rich TERRA promoter Demethylation [21]
No DNMT3b Subtelomere Methylation [130,131]
RNA − miR-290, Dicer1 4 Rbl2-dependent DNMT3a/b Upregulation [128]
+ 20q-TERRA Telomeres 3 RNA/DNA hybrids 3 [132]
Histone − TA, Tr 4 Telomeric, subtelomeric chromatin Trimethylation (H3K9, H4K20), deacetylation (H3, H4) [127]
− Suv39h1 4 Telomeric chromatin Trimethylation (H3K9) [133]
? ? Telomeric, subtelomeric chromatin Low levels of H3, H3K9me3 [126]
− ASF1a/b Chromatin 3 H3.1 and H3.3 loading 3 [57]
− ATRX Chromatin 3 ? [56]
− ATRX-DAXX Telomeric chromatin H3.3 loading [134,135]
− ? H3.3 Methylation, acetylation 5 [135]
+ CHK1 H3.3S31 Phosphorylation [136]
+ NuRD-ZNF827 Telomeric chromatin Deacetylation, decreased shelterin binding [137]
+ PML Telomeric chromatin Compaction, TRF2 depletion [138]
+ HDAC9 PML ? [139]
+ HDAC5 Telomeric chromatin ? [140]

1 Epigenetic mechanisms (EM) based on DNA, non-coding RNA or histone modifications; 2 Activating (+), inhibiting (−), neutral (No) or unknown (?) effect on ALT; 3 Suggested target or mode of action; 4 Data from mouse models; 5 Mutations K27M and G34R/V in the gene of H3.3 change the epigenetic modifications of the histone tail, which are strongly associated with ALT.