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Open Access Green as soon as Postprint is submitted to ZB.
Assembling a gene regulatory network for specification of the B cell fate.
Dev. Cell 7, 607-617 (2004)
The generation of B lymphocyte precursors is dependent on the combinatorial action of the transcription factors PU.1, Ikaros, E2A, EBF, and Pax-5. Loss of PU.1 results in a severe reduction in Flk2+, IL-7R+ lymphoid progenitors as well as impaired expression of EBF and Pax-5. Restoration of EBF expression facilitates rapid generation of pro-B cells from PU.1-/- progenitors. Molecular analysis suggests that PU.1 directly participates in regulation of the EBF gene. Although PU.1 is dispensable for expression of most early B lineage genes, it is required for CD45R/B220. Using EBF-/- mutant progenitors, we show that EBF induces Pax-5 and the early program of B lineage gene expression. Importantly, Pax-5 does not rescue B cell development from either PU.1-/- or EBF-/- progenitors. Pax-5 expression and function are contingent on EBF. Based on these results, we propose a hierarchical regulatory network for specification and commitment to the B cell fate.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2004
HGF-reported in Year
0
ISSN (print) / ISBN
1534-5807
e-ISSN
1878-1551
Journal
Developmental Cell
Quellenangaben
Volume: 7,
Issue: 4,
Pages: 607-617
Publisher
Elsevier
Reviewing status
Peer reviewed
PubMed ID
15469848
Erfassungsdatum
2004-12-31