Lymphoid Enhancer-Binding Factor-1 Binds and Activates the Recombination-Activating Gene-2 Promoter Together with c-Myb and Pax-5 in Immature B Cells
| Autor: | Atsushi Muraguchi, Shigeru Saito, Zhe-Xiong Jin, Hiroyuki Kishi, Xing-Cheng Wei, Tadashi Matsuda |
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| Rok vydání: | 2002 |
| Předmět: |
animal structures
Lymphoid Enhancer-Binding Factor 1 Macromolecular Substances Immunology Response element B-Lymphocyte Subsets Biology Transfection Recombination-activating gene Cell Line Mice Proto-Oncogene Proteins c-myb medicine Animals Humans Immunology and Allergy Binding site Promoter Regions Genetic Transcription factor Cells Cultured B cell Base Sequence PAX5 Transcription Factor Wnt signaling pathway Nuclear Proteins Cell Differentiation Drug Synergism Promoter Hematopoietic Stem Cells Molecular biology DNA-Binding Proteins body regions medicine.anatomical_structure Gene Expression Regulation embryonic structures 5' Untranslated Regions Protein Binding Transcription Factors Lymphoid enhancer-binding factor 1 |
| Zdroj: | The Journal of Immunology. 169:3783-3792 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.169.7.3783 |
| Popis: | The recombination-activating gene (RAG)-1 and RAG-2 are expressed specifically in immature lymphoid cells undergoing the recombination of Ag receptor genes. We studied the regulation of murine RAG-2 promoter and revealed that −41/−17 RAG-2 promoter region, which was indispensable for the RAG-2 promoter activity in B cell lines, contained binding sites for lymphoid enhancer-binding factor-1 (LEF-1), c-Myb, and Pax-5. We showed that these three transcription factors bound the promoter region in vitro and in vivo. Cotransfection assays using a human embryonic kidney cell line (293T) showed that LEF-1, c-Myb, and Pax-5 cooperatively activated the RAG-2 promoter, via their synergistic DNA binding. We also showed that LEF-1, c-Myb, and Pax-5 physically interact in the cells. Finally, we demonstrated that a dominant-negative LEF-1 protein, which lacks the binding site for β-catenin, suppressed the RAG-2 promoter activity as well as the endogenous RAG-2 expression in a pre-B cell line (18.81). These results suggest that LEF-1/β-catenin complex regulates the RAG-2 promoter activation in concert with c-Myb and Pax-5 in immature B cells. The link between LEF-1/β-catenin and Wnt signaling in B lineage cells will be discussed. |
| Databáze: | OpenAIRE |
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