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

Summary, in English

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.

• Författare: Eva Welinder; Robert Mansson; Elinore M. Mercer; David Bryder; Mikael Sigvardsson; Cornelis Murre
• Avdelning/ar: Reumatologi och molekylär skelettbiologi; Immunology; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 17402-17407
• Publikation/Tidskrift/Serie: Proceedings of the National Academy of Sciences
• Volym: 108
• Issue: 42
• Länkar: http://dx.doi.org/10.1073/pnas.1111766108
• Dokumenttyp: Artikel i tidskrift
• Förlag: National Academy of Sciences
• Ämne: Immunology in the medical area; Rheumatology and Autoimmunity
• Status: Published
• Forskningsgrupp: Immunology
• ISBN/ISSN/Övrigt: ISSN: 1091-6490