A dose-dependent role for EBF1 in repressing non-B-cell-specific genes
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Abstract
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.
Details
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Organisations | |
Research areas and keywords | Subject classification (UKÄ) – MANDATORY
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Original language | English |
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Pages (from-to) | 1787-1793 |
Journal | European Journal of Immunology |
Volume | 41 |
Issue number | 6 |
Publication status | Published - 2011 |
Publication category | Research |
Peer-reviewed | Yes |
Bibliographic note
The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012)