The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor
2011 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 42, 17402-17407 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
National Academy of Sciences , 2011. Vol. 108, no 42, 17402-17407 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-71775DOI: 10.1073/pnas.1111766108ISI: 000295975300039OAI: oai:DiVA.org:liu-71775DiVA: diva2:453956
Funding Agencies|National Institutes of Health||2011-11-042011-11-042011-11-04