Octamer-dependent transcription in T cells is mediated by NFAT and NF-κB

• Published in: Nucleic acids research 2013-02, Vol.41 (4), p.2138-2154
• Main Authors: Mueller, Kerstin, Quandt, Jasmin, Marienfeld, Ralf B, Weihrich, Petra, Fiedler, Katja, Claussnitzer, Melina, Laumen, Helmut, Vaeth, Martin, Berberich-Siebelt, Friederike, Serfling, Edgar, Wirth, Thomas, Brunner, Cornelia
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; Cells, Cultured; Gene Regulation, Chromatin and Epigenetics; Humans; Jurkat Cells; Mice; Mice, Inbred C57BL; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NFATC Transcription Factors - antagonists & inhibitors; NFATC Transcription Factors - metabolism; Octamer Transcription Factor-2 - biosynthesis; Octamer Transcription Factor-2 - genetics; Promoter Regions, Genetic; T-Lymphocytes - metabolism; Trans-Activators - biosynthesis; Trans-Activators - genetics; Transcription, Genetic
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gks1349

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-κB-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-κB 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-κB 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-κB transcription factors.