Runx1-Cbfβ facilitates early B lymphocyte development by regulating expression of Ebf1

Wooseok Seo, Tomokatsu Ikawa, Hiroshi Kawamoto, Ichiro Taniuchi

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Although Runx and Cbfβ transcription factor complexes are involved in the development of multiple hematopoietic lineages, their precise roles in early mouse B lymphocyte differentiation remain elusive. In this study, we examined mouse strains in which Runx1, Runx3, or Cbfβ were deleted in early B lineage progenitors by an mb1-cre transgene. Loss of Runx1, but not Runx3, caused a developmental block during early B lymphopoiesis, resulting in the lack of IgM + B cells and reduced V H to DJ H recombination. Expression of core transcription factors regulating early B cell development, such as E2A, Ebf1, and Pax5, was reduced in B cell precursors lacking Runx1. We detected binding of Runx1-Cbfβ complexes to the Ebf1 proximal promoter, and these Runx-binding motifs were essential to drive reporter gene expression. Runx1-deficient pro-B cells harbored excessive amounts of the repressive histone mark H3K27 trimethylation in the Ebf1 proximal promoter. Interestingly, retroviral transduction of Ebf1, but not Pax5, into Runx1-deficient progenitors restored not only development of B220 + cells that underwent V H to DJ H rearrangement but also expression of B lineage signature genes. Collectively, these results demonstrate that Runx1-Cbfβ complexes are essential to facilitate B lineage specification, in part via epigenetic activation of the Ebf1 gene.

Original languageEnglish
Pages (from-to)1255-1262
Number of pages8
JournalJournal of Experimental Medicine
Volume209
Issue number7
DOIs
Publication statusPublished - 02-07-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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