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  Assembling a gene regulatory network for specification of the B cell fate

Medina, K. L., Pongubala, J. M. R., Reddy, K. L., Lancki, D. W., Dekoter, R., Kieslinger, M., et al. (2004). Assembling a gene regulatory network for specification of the B cell fate. Developmental Cell, 7, 607-617. doi:10.1016/j.devcel.2004.08.006.

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Medina 2004_Dev Cell.pdf (Publisher version), 465KB
 
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Medina, Kay L1, Author
Pongubala, Jagan M R1, Author
Reddy, Karen L1, Author
Lancki, David W1, Author
Dekoter, Rodney1, Author
Kieslinger, Matthias2, Author              
Grosschedl, Rudolf2, Author              
Singh, Harinder1, Author
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1External Organizations, ou_persistent22              
2Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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 Abstract: 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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Language(s): eng - English
 Dates: 2004-10
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.devcel.2004.08.006
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Title: Developmental Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 7 Sequence Number: - Start / End Page: 607 - 617 Identifier: ISSN: 1534-5807
CoNE: https://pure.mpg.de/cone/journals/resource/111006902714134