Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells
العنوان: | Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells |
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المؤلفون: | Elizabeth M. Mandel, Ildiko Györy, Rudolf Grosschedl, Robert Nechanitzky, Sören Boller, Edison T. Liu, Sebastian Pott |
المصدر: | Genes and Development |
بيانات النشر: | Cold Spring Harbor Laboratory, 2012. |
سنة النشر: | 2012 |
مصطلحات موضوعية: | Transcription, Genetic, Cell Survival, Cellular differentiation, Mice, Transgenic, Biology, Mice, Genetics, Animals, Protein kinase B, Transcription factor, Cell Proliferation, B-Lymphocytes, CD40, Germinal center, Cell Differentiation, Cell cycle, Molecular biology, Cell biology, Mice, Inbred C57BL, B-1 cell, Gene Expression Regulation, Trans-Activators, biology.protein, Signal transduction, Immunoglobulin Heavy Chains, Genome-Wide Association Study, Signal Transduction, Research Paper, Developmental Biology |
الوصف: | The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell subsets, including B1 cells and marginal zone B cells. The proliferation defect of Ebf1-deficient pro-B cells and the impaired expression of multiple cell cycle regulators are overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with signaling via the B-cell-activating factor receptor (BAFF-R)- and B-cell receptor (BCR)-dependent Akt pathways. Moreover, Ebf1 is required for germinal center formation and class switch recombination. Genome-wide analyses of Ebf1-mediated gene expression and chromatin binding indicate that Ebf1 regulates both common and distinct sets of genes in early and late stage B cells. By regulating important components of transcription factor and signaling networks, Ebf1 appears to be involved in the coordination of cell proliferation, survival, and differentiation at multiple stages of B lymphopoiesis. |
وصف الملف: | application/pdf |
تدمد: | 1549-5477 0890-9369 |
DOI: | 10.1101/gad.187328.112 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc345aab25d30947131c57b946bbbce8 https://doi.org/10.1101/gad.187328.112 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....dc345aab25d30947131c57b946bbbce8 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15495477 08909369 |
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DOI: | 10.1101/gad.187328.112 |