| First Author | Béguelin W | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 877 |
| PubMed ID | 29026085 | Mgi Jnum | J:254397 |
| Mgi Id | MGI:6099824 | Doi | 10.1038/s41467-017-01029-x |
| Citation | Beguelin W, et al. (2017) EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop. Nat Commun 8(1):877 |
| abstractText | The EZH2 histone methyltransferase is required for B cells to form germinal centers (GC). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21(Cip1)). Deletion of Cdkn1a rescues the GC reaction in Ezh2 (-/-) mice. Using a 3D B cell follicular organoid system that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S phase transition of GC B cells in a Cdkn1a-dependent manner. GC B cells of Cdkn1a (-/-) Ezh2 (-/-) mice have high levels of phospho-Rb, indicating that loss of Cdkn1a enables progression of cell cycle. Moreover, the transcription factor E2F1 induces EZH2 during the GC reaction. E2f1 (-/-) mice manifest impaired GC responses, which is rescued by restoring EZH2 expression, thus defining a positive feedback loop in which EZH2 controls GC B cell proliferation by suppressing CDKN1A, enabling cell cycle progression with a concomitant phosphorylation of Rb and release of E2F1.The histone methyltransferase EZH2 silences genes by generating H3K27me3 marks. Here the authors use a 3D GC organoid and show EZH2 mediates germinal centre (GC) formation through epigenetic silencing of CDKN1A and release of cell cycle checkpoints. |
