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TranscriptionalRegulation of CD4Gene Expression by TCellFactor-1/β-CateninPathway Zhaofeng HuangHuimin XieVassilios Ioannidis2006 год

Transcriptional Regulation of CD4 Gene Expression by T Cell Factor-1/β-Catenin Pathway
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Аннотация: By interacting with MHC class II molecules, CD4 facilitates lineage development as well as activation of Th cells. Expression of physiological levels of CD4 requires a proximal CD4 enhancer to stimulate basic CD4 promoter activity. T cell factor (TCF)-1/beta-catenin pathway has previously been shown to regulate thymocyte survival via up-regulating antiapoptotic molecule Bcl-xL. By both loss and gain of function studies, in this study we show additional function of TCF-1/beta-catenin pathway in the regulation of CD4 expression in vivo. Mice deficient in TCF-1 displayed significantly reduced protein and mRNA levels of CD4 in CD4+ CD8+ double-positive (DP) thymocytes. A transgene encoding Bcl-2 restored survival but not CD4 levels of TCF-1(-/-) DP cells. Thus, TCF-1-regulated survival and CD4 expression are two separate events. In contrast, CD4 levels were restored on DP TCF-1(-/-) cells by transgenic expression of a wild-type TCF-1, but not a truncated TCF-1 that lacks a domain required for interacting with beta-catenin. Furthermore, forced expression of a stabilized beta-catenin, a coactivator of TCF-1, resulted in up-regulation of CD4. TCF-1 or stabilized beta-catenin greatly stimulated activity of a CD4 reporter gene driven by a basic CD4 promoter and the CD4 enhancer. However, mutation of a potential TCF binding site located within the enhancer abrogated TCF-1 and beta-catenin-mediated activation of CD4 reporter. Finally, recruitment of TCF-1 to CD4 enhancer was detected in wild-type but not TCF-1 null mice by chromatin-immunoprecipitation analysis. Thus, our results demonstrated that TCF/beta-catenin pathway enhances CD4 expression in vivo by recruiting TCF-1 to stimulate CD4 enhancer activity.
Год издания: 2006
Авторы: Zhaofeng Huang, Huimin Xie, Vassilios Ioannidis, Werner Held, Hans Clevers, Maureen Sadim, Zuoming Sun
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: Wnt/β-catenin signaling in development and cancer, Immune Cell Function and Interaction, T-cell and B-cell Immunology
Другие ссылки: The Journal of Immunology (PDF)
The Journal of Immunology (HTML)
CiteSeer X (The Pennsylvania State University) (PDF)
CiteSeer X (The Pennsylvania State University) (HTML)
PubMed (HTML)