The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor

Research output: Contribution to journalArticle

Abstract

Recent studies have identified a number of transcriptional regulators, including E proteins, EBF1, FOXO1, and PAX5, that act together to orchestrate the B-cell fate. However, it still remains unclear as to how they are linked at the earliest stages of B-cell development. Here, we show that lymphocyte development in HEB-ablated mice exhibits a partial developmental arrest, whereas B-cell development in E2A(+/-)HEB(-/)-mice is completely blocked at the LY6D(-) common lymphoid progenitor stage. We show that the transcription signatures of E2A-and HEB-ablated common lymphoid progenitors significantly overlap. Notably, we found that Foxo1 expression was substantially reduced in the LY6D-HEB-and E2A-deficient cells. Finally, we show that E2A binds to enhancer elements across the FOXO1 locus to activate Foxo1 expression, linking E2A and FOXO1 directly in a common pathway. In summary, the data indicate that the earliest event in B-cell specification involves the induction of FOXO1 expression and requires the combined activities of E2A and HEB.

Details

Authors
  • Eva Welinder
  • Robert Mansson
  • Elinore M. Mercer
  • David Bryder
  • Mikael Sigvardsson
  • Cornelis Murre
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
  • Rheumatology and Autoimmunity
Original languageEnglish
Pages (from-to)17402-17407
JournalProceedings of the National Academy of Sciences
Volume108
Issue number42
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151), Immunology (013212020)

Related research output

Welinder, E., 2012, Section for Immunology, Lund University. 109 p.

Research output: ThesisDoctoral Thesis (compilation)

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