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

Författare:
  • Kara Lukin
  • Scott Fields
  • Lisa Guerrettaz
  • Desiree Straign
  • Valerie Rodriguez
  • Sasan Zandi
  • Robert Månsson
  • John C. Cambier
  • Mikael Sigvardsson
  • James Hagman
Publiceringsår: 2011
Språk: Engelska
Sidor: 1787-1793
Publikation/Tidskrift/Serie: European Journal of Immunology
Volym: 41
Nummer: 6
Dokumenttyp: Artikel
Förlag: Wiley-Blackwell

Sammanfattning

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.

Disputation

Nyckelord

  • Medicine and Health Sciences
  • B-cell development
  • Gene regulation
  • NK cells
  • Transcription factors

Övriga

Published
Yes
  • ISSN: 0014-2980

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