A dose-dependent role for EBF1 in repressing non-B-cell-specific genes.

Eur J Immunol 2011 Jun 9;41(6):1787-93. Epub 2011 May 9.

Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.201041137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127254PMC
June 2011
5 Reads

Publication Analysis

Top Keywords

erhet mice
12
cells erhet
8
non-b-cell-specific genes
8
ebf1
6
expression
5
effects exacerbated
4
phenotype effects
4
undifferentiated phenotype
4
ly6a/sca-1 suggested
4
suggested maintenance
4
maintenance undifferentiated
4
exacerbated reduced
4
expression pax5
4
occurred despite
4
despite expression
4
runx1 occurred
4
expression runx1
4
reduced expression
4
expression ly6a/sca-1
4
b-cell progenitors
4

Similar Publications