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The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor
University of California San Diego.
University of California San Diego.
University of California San Diego.
Lund University.
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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
Abstract [en]

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.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71775DOI: 10.1073/pnas.1111766108ISI: 000295975300039OAI: oai:DiVA.org:liu-71775DiVA: diva2:453956
Note
Funding Agencies|National Institutes of Health||Available from: 2011-11-04 Created: 2011-11-04 Last updated: 2017-12-08

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Sigvardsson, Mikael

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Experimental HematologyFaculty of Health Sciences
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CiteExportLink to record
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Citation style
  • apa
  • harvard1
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  • Other style
More styles
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  • de-DE
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