TY  - JOUR
A1  - Mueller, Kerstin
A1  - Quandt, Jasmin
A1  - Marienfeld, Ralf B.
A1  - Weihrich, Petra
A1  - Fiedler, Katja
A1  - Claussnitzer, Melina
A1  - Laumen, Helmut
A1  - Vaeth, Martin
A1  - Berberich-Siebelt, Frederike
A1  - Serfling, Edgar
A1  - Wirth, Thomas
A1  - Brunner, Cornelia
T1  - Octamer-dependent transcription in T cells is mediated by NFAT and \(NF-\kappa B\)
JF  - Nucleic Acids Research
N2  - 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 \(Ca^{2+}\)/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.
KW  - germinal center formation
KW  - OBF-1 OCA-B
KW  - coactivator OBF-1
KW  - gene expression
KW  - functional characterization
KW  - immunoglobulin promoters
KW  - OCT-1-deficient mice
KW  - embryonic lethality
KW  - endothelial cells
KW  - murine homolog
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123280
SN  - 1362-4962
VL  - 41
IS  - 4
ER  -