title: Octamer-dependent transcription in T cells is mediated by NFAT and NF-κB.
abstract: 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.
authors.affiliation: Institute of Physiological Chemistry, University Ulm, D-89081 Ulm, Germany, Institute of Pathology, University Ulm, D-89081 Ulm, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Mueller
authors.forename: Jasmin
authors.initials: J
authors.lastname: Quandt
authors.forename: Ralf B
authors.initials: RB
authors.lastname: Marienfeld
authors.forename: Petra
authors.initials: P
authors.lastname: Weihrich
authors.forename: Katja
authors.initials: K
authors.lastname: Fiedler
authors.forename: Melina
authors.initials: M
authors.lastname: Claussnitzer
authors.forename: Helmut
authors.initials: H
authors.lastname: Laumen
authors.forename: Martin
authors.initials: M
authors.lastname: Vaeth
authors.forename: Friederike
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: Edgar
authors.initials: E
authors.lastname: Serfling
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.forename: Cornelia
authors.initials: C
authors.lastname: Brunner
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050813:Octamer Transcription Factor-2 / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; D050778:NFATC Transcription Factors; D050813:Octamer Transcription Factor-2; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators