Journal
NUCLEIC ACIDS RESEARCH
Volume 41, Issue 4, Pages 2138-2154Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gks1349
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [DFG] [TR52, TP A3, BR-2891/4-1]
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The transcriptional co-activator BOB.1/OBF.1 was originally identified in B cells and is constitutively expressed throughout B cell development. BOB.1/OBF.1 associates with the transcription factors Oct1 and Oct2, thereby enhancing octamer-dependent transcription. In contrast, in T cells, BOB.1/OBF.1 expression is inducible by treatment of cells with PMA/Ionomycin or by antigen receptor engagement, indicating a marked difference in the regulation of BOB.1/OBF.1 expression in B versus T cells. The molecular mechanisms underlying the differential expression of BOB.1/OBF.1 in T and B cells remain largely unknown. Therefore, the present study focuses on mechanisms controlling the transcriptional regulation of BOB.1/OBF.1 and Oct2 in T cells. We show that both calcineurin- and NF-kappa B-inhibitors efficiently attenuate the expression of BOB.1/OBF.1 and Oct2 in T cells. In silico analyses of the BOB.1/OBF.1 promoter revealed the presence of previously unappreciated combined NFAT/NF-kappa B sites. An array of genetic and biochemical analyses illustrates the involvement of the Ca2+/calmodulin-dependent phosphatase calcineurin as well as NFAT and NF-kappa B transcription factors in the transcriptional regulation of octamer-dependent transcription in T cells. Conclusively, impaired expression of BOB.1/OBF.1 and Oct2 and therefore a hampered octamer-dependent transcription may participate in T cell-mediated immunodeficiency caused by the deletion of NFAT or NF-kappa B transcription factors.
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