| First Author | Lio CW | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27869616 | Mgi Jnum | J:239176 |
| Mgi Id | MGI:5825400 | Doi | 10.7554/eLife.18290 |
| Citation | Lio CW, et al. (2016) Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility. Elife 5:e18290 |
| abstractText | Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igkappa locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igkappa 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igkappa enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igkappa enhancer function by modulating the modification status of DNA. |
