Octamer-binding factor 6 (Oct-6/Pou3f1) is induced by interferon and contributes to dsRNA-mediated transcriptional responses.
BACKGROUND
Octamer-binding factor 6 (Oct-6, Pou3f1, SCIP, Tst-1) is a transcription factor of the Pit-Oct-Unc (POU) family. POU proteins regulate key developmental processes and have been identified from a diverse range of species. Oct-6 expression is described to be confined to the developing brain, Schwann cells, oligodendrocyte precursors, testes, and skin. Its function is primarily characterised in Schwann cells, where it is required for correctly timed transition to the myelinating state. In the present study, we report that Oct-6 is an interferon (IFN)-inducible protein and show for the first time expression in murine fibroblasts and macrophages.


RESULTS
Oct-6 was induced by type I and type II IFN, but not by interleukin-6. Induction of Oct-6 after IFNbeta treatment was mainly dependent on signal transducer and activator of transcription 1 (Stat1) and partially on tyrosine kinase 2 (Tyk2). Chromatin immunopreciptitation experiments revealed binding of Stat1 to the Oct-6 promoter in a region around 500 bp upstream of the transcription start site, a region different from the downstream regulatory element involved in Schwann cell-specific Oct-6 expression. Oct-6 was also induced by dsRNA treatment and during viral infections, in both cases via autocrine/paracrine actions of IFNalpha/beta. Using microarray and RT-qPCR, we furthermore show that Oct-6 is involved in the regulation of transcriptional responses to dsRNA, in particular in the gene regulation of serine/threonine protein kinase 40 (Stk40) and U7 snRNA-associated Sm-like protein Lsm10 (Lsm10).


CONCLUSIONS
Our data show that Oct-6 expression is not as restricted as previously assumed. Induction of Oct-6 by IFNs and viruses in at least two different cell types, and involvement of Oct-6 in gene regulation after dsRNA treatment, suggest novel functions of Oct-6 in innate immune responses.
Hofmann
Elisabeth
E
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
Reichart
Ursula
U
Gausterer
Christian
C
Guelly
Christian
C
Meijer
Dies
D
Müller
Mathias
M
Strobl
Birgit
B
D000818:Animals; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D007113:Immunity, Innate / Q000235:genetics; D016899:Interferon-beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D009024:Morphogenesis / Q000235:genetics; D050816:Octamer Transcription Factor-6 / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012330:RNA, Double-Stranded / Q000494:pharmacology; D012367:RNA, Viral / Q000494:pharmacology; D020885:Ribonucleoprotein, U7 Small Nuclear / Q000096:biosynthesis / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D012330:RNA, Double-Stranded; D012367:RNA, Viral; D020885:Ribonucleoprotein, U7 Small Nuclear; D050794:STAT1 Transcription Factor; D050816:Octamer Transcription Factor-6; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases; C547661:Stk40 protein, mouse