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- W4313331004 abstract "Abstract Induction of isotype switching to a particular C(H) gene correlates with the transcriptional activation of the same gene in germline configuration. Induction of correctly spliced germline transcripts is necessary to target a switch region for recombination and switching. Different cytokines activate transcription at different germline promoters. Because binding sites for the B cell-specific transcription factor BSAP are located upstream of several switch regions in the Ig locus, BSAP might play a role in isotype switching by regulating germline transcription. We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells. We identified human EBV-negative B cell lines that express epsilon germline transcripts upon stimulation with IL-4. Electrophoretic mobility shift assay analysis showed that the human epsilon germline promoter binds BSAP. BSAP activity was expressed constitutively and was not affected by stimulation with IL-4 and/or anti-CD40 mAb. Reporter assays with constructs containing a luciferase gene driven by the epsilon germline promoter, with or without mutations in the BSAP binding site, showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated up-regulation of human epsilon germline transcription. Furthermore, epsilon germline promoter activity was abrogated in REH cells that express a BSAP polypeptide truncated in the trans-activation domain. Among the transcription factors that regulate epsilon germline expression, BSAP is unique, in that it is B cell-specific and is at the merging point of two signaling pathways that are distinct but both critical for the induction of IgE switching." @default.
- W4313331004 created "2023-01-06" @default.
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- W4313331004 date "1997-06-15" @default.
- W4313331004 modified "2023-10-16" @default.
- W4313331004 title "The transcription factor B cell-specific activator protein (BSAP) enhances both IL-4- and CD40-mediated activation of the human epsilon germline promoter." @default.
- W4313331004 doi "https://doi.org/10.4049/jimmunol.158.12.5874" @default.
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