| First Author | Aslam MA | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 2 | Pages | e51184 |
| PubMed ID | 33410591 | Mgi Jnum | J:302303 |
| Mgi Id | MGI:6507683 | Doi | 10.15252/embr.202051184 |
| Citation | Aslam MA, et al. (2021) Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation. EMBO Rep 22(2):e51184 |
| abstractText | Differentiation of naive peripheral B cells into terminally differentiated plasma cells is characterized by epigenetic alterations, yet the epigenetic mechanisms that control B-cell fate remain unclear. Here, we identified a role for the histone H3K79 methyltransferase DOT1L in controlling B-cell differentiation. Mouse B cells lacking Dot1L failed to establish germinal centers (GC) and normal humoral immune responses in vivo. In vitro, activated B cells in which Dot1L was deleted showed aberrant differentiation and prematurely acquired plasma cell characteristics. Similar results were obtained when DOT1L was chemically inhibited in mature B cells in vitro. Mechanistically, combined epigenomics and transcriptomics analysis revealed that DOT1L promotes expression of a pro-proliferative, pro-GC program. In addition, DOT1L indirectly supports the repression of an anti-proliferative plasma cell differentiation program by maintaining the repression of Polycomb Repressor Complex 2 (PRC2) targets. Our findings show that DOT1L is a key modulator of the core transcriptional and epigenetic landscape in B cells, establishing an epigenetic barrier that warrants B-cell naivety and GC B-cell differentiation. |
