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

Lukin, Kara; Fields, Scott; Guerrettaz, Lisa; Straign, Desiree; Rodriguez, Valerie; Zandi, Sasan; Månsson, Robert LU ; Cambier, John C.; Sigvardsson, Mikael LU and Hagman, James (2011) In European Journal of Immunology 41(6). p.1787-1793
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
B-cell development, Gene regulation, NK cells, Transcription factors
in
European Journal of Immunology
volume
41
issue
6
pages
1787 - 1793
publisher
John Wiley & Sons
external identifiers
  • wos:000291559700028
  • scopus:79957559436
ISSN
1521-4141
DOI
10.1002/eji.201041137
language
English
LU publication?
yes
id
e3722af8-b6c3-4c08-b0a4-8e23ed188962 (old id 1984951)
date added to LUP
2011-07-01 09:12:01
date last changed
2017-01-29 03:02:14
@article{e3722af8-b6c3-4c08-b0a4-8e23ed188962,
  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.},
  author       = {Lukin, Kara and Fields, Scott and Guerrettaz, Lisa and Straign, Desiree and Rodriguez, Valerie and Zandi, Sasan and Månsson, Robert and Cambier, John C. and Sigvardsson, Mikael and Hagman, James},
  issn         = {1521-4141},
  keyword      = {B-cell development,Gene regulation,NK cells,Transcription factors},
  language     = {eng},
  number       = {6},
  pages        = {1787--1793},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {A dose-dependent role for EBF1 in repressing non-B-cell-specific genes},
  url          = {http://dx.doi.org/10.1002/eji.201041137},
  volume       = {41},
  year         = {2011},
}