Table 2.
Experimental studies employing molecular tools to modify polycomb group (PcG) components and thereby affect human cell growth regulation.
| TSG Target | “Reader/Writer/Erasers” Experimentally Perturbed | Experimental Perturbation | PRC or Histone Mark Verification | Cell Model | Adverse Phenotype Modified by Perturbation: ← Reversal of Oncogenic Phenotype; → Enhancement of Oncogenic Phenotype | Reference |
|---|---|---|---|---|---|---|
| p16/INK4A | SUZ12, CBX8, BMI1; mRNA down-regulation; loss of binding to p16 locus | Knockdown (stable shRNA expression from retroviral vector) | Knockdowns of CBX8 or BMI1 reduced the recruitment of both proteins and the p16/INK4A locus | TIG3-T telomerase-immortalized human fibroblasts | ← p16 up-regulation with decrease growth of TIG3-T cells and reduction of colony formation in U2OS cells | [91] |
| p16/INK4A | JMJD3 (H3K27me3 demethylase) down-regulation or up-regulation | Knockdown (stable shRNA expression from retroviral vector); up-regulation by ectopic expression | Exogenous JMJD3 was recruited to the p16/INK4A locus, caused reduction in H3K27me3 | 1° human fibroblasts | → p16 down-regulation and partial bypass of RAS oncogene-induced senescence response ← Induced senescence |
[92] |
| p16/INK4A and ARF | CBX7 up-regulation/down-regulation | Over expression and knockdown (stable shRNA expression from retroviral vector) | No measures of changes to CBX7 abundance at p16 or ARF loci | Variety of human 1° cells | → CBX7 overexpression causes p16 down-regulation and extended replicative capacity CBX7 repression caused severely impaired growth |
[93] |
| p16/INK4A | BMI1 up-regulation | Overexpression by expression vector transfection | No measures of histone ubiquitination on p16/INK4A chromatin | 1° human mammary epithelial cells | → BMI1 overexpression suppressed p16/INK4A expression and weakly induced hTERT activity; p16/INK4A was shown to be required replicative lifetime extension | [94] |