| First Author | Lukin K | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 6 | Pages | 1787-93 |
| PubMed ID | 21469119 | Mgi Jnum | J:176486 |
| Mgi Id | MGI:5291903 | Doi | 10.1002/eji.201041137 |
| Citation | Lukin K, et al. (2011) A dose-dependent role for EBF1 in repressing non-B-cell-specific genes. Eur J Immunol 41(6):1787-93 |
| abstractText | In the absence of early B-cell factor 1 (EBF1), B-cell development is arrested at an uncommitted progenitor stage that exhibits increased lineage potentials. Previously, we investigated the roles of EBF1 and its DNA-binding partner Runx1 by evaluating B lymphopoiesis in single (EBF1(het) and Runx1(het)) and compound haploinsufficent (Ebf1(+/-) Runx1(+/-), ER(het)) mice. Here, we demonstrate that decreased Ebf1 gene dosage results in the inappropriate expression of NK-cell lineage-specific genes in B-cell progenitors. Moreover, prolonged expression of Ly6a/Sca-1 suggested the maintenance of a relatively undifferentiated phenotype. These effects were exacerbated by reduced expression of Runx1 and occurred despite expression of Pax5. Repression of inappropriately expressed genes was restored in most pre-B and all immature B cells of ER(het) mice. Enforced EBF1 expression repressed promiscuous transcription in pro-B cells of ER(het) mice and in Ebf1(-/-) Pax5(-/-) fetal liver cells. Together, our studies suggest that normal levels of EBF1 are critical for maintaining B-cell identity by directing repression of non-B-cell-specific genes. |
