A dose-dependent role for EBF1 in repressing non-B-cell-specific genes
Author
Summary, in English
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(+/-), ERhet) 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 ERhet mice. Enforced EBF1 expression repressed promiscuous transcription in pro-B cells of ERhet 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.
Publishing year
2011
Language
English
Pages
1787-1793
Publication/Series
European Journal of Immunology
Volume
41
Issue
6
Document type
Journal article
Publisher
John Wiley & Sons Inc.
Topic
- Immunology in the medical area
Keywords
- B-cell development
- Gene regulation
- NK cells
- Transcription factors
Status
Published
ISBN/ISSN/Other
- ISSN: 1521-4141