A dose-dependent role for EBF1 in repressing non-B-cell-specific genes
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1984951
- author
- Lukin, Kara ; Fields, Scott ; Guerrettaz, Lisa ; Straign, Desiree ; Rodriguez, Valerie ; Zandi, Sasan ; Månsson, Robert LU ; Cambier, John C. ; Sigvardsson, Mikael LU and Hagman, James
- organization
- publishing date
- 2011
- 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 Inc.
- external identifiers
-
- wos:000291559700028
- scopus:79957559436
- pmid:21469119
- ISSN
- 1521-4141
- DOI
- 10.1002/eji.201041137
- language
- English
- LU publication?
- yes
- additional info
- 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)
- id
- e3722af8-b6c3-4c08-b0a4-8e23ed188962 (old id 1984951)
- date added to LUP
- 2016-04-01 09:55:55
- date last changed
- 2022-08-27 04:44:35
@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}}, keywords = {{B-cell development; Gene regulation; NK cells; Transcription factors}}, language = {{eng}}, number = {{6}}, pages = {{1787--1793}}, publisher = {{John Wiley & Sons Inc.}}, 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}}, doi = {{10.1002/eji.201041137}}, volume = {{41}}, year = {{2011}}, }