Table 1.
Genetic Approaches to Study Mechanisms of DNA Methylation
| Species | Disrupted Gene(s) | Change in DNA Methylation | Sequence Specificity | Somatic Phenotype | Reference |
|---|---|---|---|---|---|
| Mouse Germ Cells | Dnmt3a | ↓ | H19, Dlk1/Gtl2, and SineB1 also Rasgrf1, IAPs and Line 1 | 63 | |
| Dnmt3b | ↓ | Satellites, IAPs, Line 1 and Rasgrf1 | 63 | ||
| Dnmt3L | ↓ | All of above sequences | 63,64 | ||
| Mouse Embryonic Stem Cells and Embryos | Dnmt 1 | ∼80% ↓ | Non specific | Lethal; (p53-dependent apoptosis in somatic cells) | 8,22,65 |
| Dnmt 3a | No change | N/A | Lethal (postnatal) | 8 | |
| Dnmt 3b | Not dramatic | Centromeric repeats ↓ | Lethal | 8 | |
| Dnmt 3a & 3b | 20% ↓ and ↑ hemi-methylation | Imprined genes↓ Repeats ↓ | Lethal | 7,8 | |
| Dnmt 1/3a/3b | No DNA methylation | All CpG sites | N/A | 66 | |
| Dnmt3L | Altered | Imprinted genes ↓ | Sterile in both sexes | 67 | |
| Dnmt 2 | No change | tRNA methylation | None | 68,69 | |
| G9a | Dramatic ↓ | Repeats ↓ | Lethal | 43,70 | |
| UHRF1 (Np95) | ∼80% ↓ | Hemi-methylated sites ↑ | Lethal (gastrulation) | 20 | |
| Lsd1 | ∼40% ↓ | Non specific | Lethal (gastrulation) | 71 | |
| Lsh | 45-67% ↓ | Non specific | Lethal (perinatal) | 53 | |
| Human Somatic Cells | DNMT1 | ↑ Hemi-methylation | CpG poor ↓ | Lethal in somatic cells | 38,72,73 |
| DNMT3B (HCT116) | Not dramatic | Non specific | ICF | 74 | |
| DNMT1 (hypomorphs) and 3B | Dramatic ↓ | Non specific | N/A | 74 |