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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Eva Welinder
  • Robert Mansson
  • Elinore M. Mercer
  • David Bryder
  • Mikael Sigvardsson
  • Cornelis Murre
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
  • Reumatologi och inflammation
Originalspråkengelska
Sidor (från-till)17402-17407
TidskriftProceedings of the National Academy of Sciences
Volym108
Utgåva nummer42
StatusPublished - 2011
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

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

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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