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  Distinct Promoters Mediate the Regulation of Ebf1 Gene Expression by Interleukin-7 and Pax5

Roessler, S., Györy, I., Imhof, S., Spivakov, M., Williams, R. R., Busslinger, M., et al. (2007). Distinct Promoters Mediate the Regulation of Ebf1 Gene Expression by Interleukin-7 and Pax5. Molecular and Cellular Biology (Washington, DC), 27, 579-594. doi:10.1128/MCB.01192-06.

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Roessler 2007_Mol Cell Biol.pdf (Publisher version), 789KB
 
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Roessler, Stephanie1, Author              
Györy, Ildiko1, Author              
Imhof, Sascha1, Author              
Spivakov, Mikhail2, Author
Williams, Ruth R.2, Author
Busslinger, Meinrad2, Author
Fischer, Amanda G.2, Author
Grosschedl, Rudolf1, Author              
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1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2External Organizations, ou_persistent22              

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 Abstract: Early differentiation of B lymphocytes requires the function of multiple transcription factors that regulate the specification and commitment of the lineage. Loss- and gain-of-function experiments have provided important insight into the transcriptional control of B lymphopoiesis, whereby E2A was suggested to act upstream of EBF1 and Pax5 downstream of EBF1. However, this simple hierarchy cannot account for all observations, and our understanding of a presumed regulatory network, in which transcription factors and signaling pathways operate, is limited. Here, we show that the expression of the Ebf1 gene involves two promoters that are differentially regulated and generate distinct protein isoforms. We find that interleukin-7 signaling, E2A, and EBF1 activate the distal Ebf1 promoter, whereas Pax5, together with Ets1 and Pu.1, regulates the stronger proximal promoter. In the absence of Pax5, the function of the proximal Ebf1 promoter and accumulation of EBF1 protein are impaired and the replication timing and subcellular localization of the Ebf1 locus are altered. Taken together, these data suggest that the regulation of Ebf1 via distinct promoters allows for the generation of several feedback loops and the coordination of multiple determinants of B lymphopoiesis in a regulatory network.

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Language(s): eng - English
 Dates: 2007-01
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1128/MCB.01192-06
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Title: Molecular and Cellular Biology (Washington, DC)
  Other : Mol Cell Biol
Source Genre: Journal
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Publ. Info: American Society for Microbiology (ASM)
Pages: - Volume / Issue: 27 Sequence Number: - Start / End Page: 579 - 594 Identifier: ISSN: 0270-7306
CoNE: https://pure.mpg.de/cone/journals/resource/954925502188