Octamer-binding factor 6 (Oct-6/Pou3f1) is induced by interferon and contributes to dsRNA-mediated transcriptional responses

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>Oct-6 was induced by type I and type II IFN, but not by interleukin-6. Induction of Oct-6 after IFNβ 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 <it>via </it>autocrine/paracrine actions of IFNα/β. 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 (<it>Stk40</it>) and U7 snRNA-associated Sm-like protein Lsm10 (<it>Lsm10)</it>.</p> <p>Conclusion</p> <p>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.</p

TYK2 Kinase Activity Is Required for Functional Type I Interferon Responses In Vivo

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in cytokine signalling. In vitro analyses suggest that TYK2 also has kinase-independent, i.e., non-canonical, functions. We have generated gene-targeted mice harbouring a mutation in the ATP-binding pocket of the kinase domain. The Tyk2 kinase-inactive (Tyk2K923E) mice are viable and show no gross abnormalities. We show that kinase-active TYK2 is required for full-fledged type I interferon- (IFN) induced activation of the transcription factors STAT1-4 and for the in vivo antiviral defence against viruses primarily controlled through type I IFN actions. In addition, TYK2 kinase activity was found to be required for the protein’s stability. An inhibitory function was only observed upon over-expression of TYK2K923E in vitro. Tyk2K923E mice represent the first model for studying the kinase-independent function of a JAK in vivo and for assessing the consequences of side effects of JAK inhibitors

Testosterone increases risk-taking for status but not for money

Testosterone has long been thought to increase risk-taking, but evidence supporting this association is mixed. Instead, testosterone’s key role may be to promote status-seeking behaviors. Here, we examined to what extent testosterone administration affects risk preferences for both monetary and social status outcomes, and whether this relationship is moderated by an individuals’ social status. Male participants (N=166) experienced high or low status in a competition task and then played two risk tasks; one involving gambles with only monetary outcomes, and another one involving gambles with non-monetary outcomes that influenced their social rank. We found that testosterone (vs. placebo) altered risk preferences for gains and losses in social rank, but not for monetary gains and losses. Specifically, testosterone increased risk-taking to increase social rank in individuals with high, but not low social status. These results demonstrate a context-dependent role of testosterone in regulating risk-taking for social status