| First Author | Zhang X | Year | 2016 |
| Journal | Nat Genet | Volume | 48 |
| Issue | 9 | Pages | 1014-23 |
| PubMed ID | 27428748 | Mgi Jnum | J:274091 |
| Mgi Id | MGI:6141602 | Doi | 10.1038/ng.3610 |
| Citation | Zhang X, et al. (2016) DNMT3A and TET2 compete and cooperate to repress lineage-specific transcription factors in hematopoietic stem cells. Nat Genet 48(9):1014-23 |
| abstractText | Mutations in the epigenetic modifiers DNMT3A and TET2 non-randomly co-occur in lymphoma and leukemia despite their epistasis in the methylation-hydroxymethylation pathway. Using Dnmt3a and Tet2 double-knockout mice in which the development of malignancy is accelerated, we show that the double-knockout methylome reflects regions of independent, competitive and cooperative activity. Expression of lineage-specific transcription factors, including the erythroid regulators Klf1 and Epor, is upregulated in double-knockout hematopoietic stem cells (HSCs). DNMT3A and TET2 both repress Klf1, suggesting a model of cooperative inhibition by epigenetic modifiers. These data demonstrate a dual role for TET2 in promoting and inhibiting HSC differentiation, the loss of which, along with DNMT3A, obstructs differentiation, leading to transformation. |
