| First Author | Seo W | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 7 | Pages | 1255-62 |
| PubMed ID | 22665574 | Mgi Jnum | J:189102 |
| Mgi Id | MGI:5444347 | Doi | 10.1084/jem.20112745 |
| Citation | Seo W, et al. (2012) Runx1-Cbfbeta facilitates early B lymphocyte development by regulating expression of Ebf1. J Exp Med 209(7):1255-62 |
| abstractText | Although Runx and Cbfbeta transcription factor complexes are involved in the development of multiple hematopoietic lineages, their precise roles in early mouse B lymphocyte differentiation remain elusive. In this study, we examined mouse strains in which Runx1, Runx3, or Cbfbeta were deleted in early B lineage progenitors by an mb1-cre transgene. Loss of Runx1, but not Runx3, caused a developmental block during early B lymphopoiesis, resulting in the lack of IgM(+) B cells and reduced V(H) to DJ(H) recombination. Expression of core transcription factors regulating early B cell development, such as E2A, Ebf1, and Pax5, was reduced in B cell precursors lacking Runx1. We detected binding of Runx1-Cbfbeta complexes to the Ebf1 proximal promoter, and these Runx-binding motifs were essential to drive reporter gene expression. Runx1-deficient pro-B cells harbored excessive amounts of the repressive histone mark H3K27 trimethylation in the Ebf1 proximal promoter. Interestingly, retroviral transduction of Ebf1, but not Pax5, into Runx1-deficient progenitors restored not only development of B220(+) cells that underwent V(H) to DJ(H) rearrangement but also expression of B lineage signature genes. Collectively, these results demonstrate that Runx1-Cbfbeta complexes are essential to facilitate B lineage specification, in part via epigenetic activation of the Ebf1 gene. |
