| First Author | Mandal M | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3888 |
| PubMed ID | 30250168 | Mgi Jnum | J:268344 |
| Mgi Id | MGI:6267562 | Doi | 10.1038/s41467-018-06165-6 |
| Citation | Mandal M, et al. (2018) BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis. Nat Commun 9(1):3888 |
| abstractText | Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. Here we show that in small pre-B cells, the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding. BRWD1 regulates over 7000 genes to repress proliferative and induce differentiation programs. However, BRWD1 does not regulate the expression of TFs required for B lymphopoiesis. Hypogammaglobulinemia patients with BRWD1 mutations have B-cell transcriptional profiles and enhancer landscapes similar to those observed in Brwd1(-/-) mice. These data indicate that, in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with TF networks to drive late B-cell development. |
