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| Item Type: | Article |
|---|---|
| Title: | Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation |
| Creators Name: | Aslam, M.A., Alemdehy, M.F., Kwesi-Maliepaard, E.M., Muhaimin, F.I., Caganova, M., Pardieck, I.N., van den Brand, T., van Welsem, T., de Rink, I., Song, J.Y., de Wit, E., Arens, R., Jacobs, H. and van Leeuwen, F. |
| Abstract: | Differentiation of naïve 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. |
| Keywords: | B-Cell Differentiation, DOT1L, Germinal Center B Cell, Plasma Cell, PRC2, Animals, Mice |
| Source: | EMBO Reports |
| ISSN: | 1469-221X |
| Publisher: | EMBO Press / Wiley |
| Volume: | 22 |
| Number: | 2 |
| Page Range: | e51184 |
| Date: | 3 February 2021 |
| Official Publication: | https://doi.org/10.15252/embr.202051184 |
| PubMed: | View item in PubMed |
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