Table 1. Survey of methylation stability of imprinted genes.
| Imprinted genes | Growth-related genes | Neuronal genes | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Igf2 | H19 | Meg1/Grb10 | U2af1-rs1a | Igf2r | Peg1/Mest | P57Kip2 | Snrpn | Ndn | Peg3 | |
| Imposed in vitro stress factors | ||||||||||
| Passaging/culturing | +5,8,11,13 | +5,6,7,8,13 | +5 | +8 | +8 | *5 | *1,15 | *1 | ||
| NT | +3 | +3+16 | +3 | *3+16 | +3 | *3 | *3+16 | |||
| Transgenes | +4 | *1 | *1 | |||||||
| ES differentiation | +3 | *1 | *1 | |||||||
| ES cell clones | +3 | +3 | *1 | *1 | ||||||
| Spermatid injection | +12 | |||||||||
| Epigenetic instability after treatment with factors that influence the imprint machinery | ||||||||||
| TSA treatment | +9 | +10 | +9 | *9,10 | *9 | |||||
| AcaC/TSA treatment | +9 | *9 | +9 | *9 | +9 | *9 | +9 | |||
| Dnmt1 over-expression | +2 | +2 | *2 | *2 | *2 | |||||
| Epigenetic instability and carcinogenesis | ||||||||||
| Tumors | +x | +x | +14 | +1 | ||||||
Some imprinted genes may be particularly susceptible to epigenetic changes, which occur during pre-implantation development. Reported epigenetic instability (+) and epigenetic stability (*) of cultured mammalian pre-implantation stage embryos, fibroblasts, primary T-lymphocyte clones, spermatids, ES cells and ES cell-derived clones. TSA inhibits histone-deacetylases. 1Schumacher et al. (22), this study; 2Cox et al. (64); 3Humpherys et al. (2); 4Mueller et al. (38); 5Khosla et al. (21); 6Doherty et al. (66); 7Sasaki et al. (20); 8Dean et al. (1); 9Kharroubi et al. (67); 10Gregory et al. (68); 11Blondin et al. (69); 12Shamanski et al. (70); 13Ungaro et al. (71); 14Miura et al. (72); 15LaSalle et al. (73); 16Mann et al. (3); x, several reports.
aThe exact influence of the splice-factor U2af1-rs1 on embryonal growth remains to be elucidated, however, mice with maternal and paternal disomy for chromosome 11 show abnormal growth phenotypes (74).