Table 2.
Histone modifications of the TERT promoter.
Histone Modification | Associated Mechanism | Cell Type | Reference |
---|---|---|---|
H3K4Me3, H3K9Ac, H3Ac H4Ac (Active marks) H3K9Me3, H4K20Me (Repressive) |
The lowest expression of repressive marks but the highest levels of active marks in the cell lines expressing high levels of TERT Higher levels of repressive marks at the promoter in ALT cell lines |
WI38, SUSM-1, KMST-6, and WI38-SV40 (ALT cells lines) C33a, A2780, and 5637 (high TERT expression) | [163] |
H3K4Me2/3 (Active marks) | Increase occupancy of MYC and SP1 on the TERT promoter | HCT116 and L1236 cells | [156] |
H3K9Ac, H3K4Me2 (Active marks) H3K9me3, H3K27me3 (Repressive) | Both active and inactive chromatin signs present across the TERT promoter | RKO, SW480, HCT 116, MCF7, and VA13 cells | [136] |
H3K9Ac (Active marks) H3K9Me3 (Repressive) | Depletion of SIRT1 induces H3K9Ac and reduce H3K9Me3 at TERT | Hepatocellular carcinoma | [168] |
H3K4Me2/3 (Active marks) H3K27me3 (Repressive) | Mutant TERT promoters exhibit the H3K4me2/3 and recruit the GABPA/B1 transcription factor in multiple cancer cell lines, while the wild-type allele exhibits the H3K27me3 | HepG2, SNU-475, SNU-423, UMUC3 and T24 | [76] |
H3K4Me3, H3K9Ac (Active marks) | Enrichment of both H3K4Me3 and H3K9Ac in the proximal TERT promoter region in mutant cell lines | BLM, A375, T98G (bearing -146 C>T mutation), and U251 (bearing −124 C>T mutation) | [161] |
H3K4Me3 (Active mark) | Increased H3K4Me3 allows MYC/MAX binding to E-boxes in the TERT promoter | E6E7 IDH1mut pre- and postcrisis cells | [160] |
H3K27Me1, H3K27ac (Active marks) H3K27me3 (Repressive) |
Enrichment of active marks in the juxtaposed to the TERT promoter | NIH Roadmap Epigenomics Consortium (111 epigenomes) | [15] |
H3K4me3, H4Ac (Active marks) H3K9Me3 H3K27me3 (Repressive) | TERT silencing during differentiation accompanied by increases of repressive marks | Human embryonic stem cell | [159] |
H3K4me3 (Active mark) H3K27me3, HP-1α (Repressive) | H3K4me3 is enriched in iPSCs, whereas H3K27me3 and HP-1α levels are higher in somatic cells | Fetal lung fibroblast (MRC) and MRC-iPSCs | [135] |
H3K4Me3, H3Ac (Active marks) H3K27Me3 (Repressive) | Active marks are enriched at TERT core promoter | Acute promyelocytic leukemia cells NB4-LR1 and NB4-LR1 | [169] |