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

Hofmann, Elisabeth; Reichart, Ursula; Gausterer, Christian; Godballe, Christian; Meijer, Dies; Müller, Mathias; Strobl, Birgit

doi:10.1186/1471-2121-11-61

Cited by 15 publications

(12 citation statements)

References 69 publications

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“…Here, we also detected partially conserved sites belonging to the category “brain/CNS transcription factors,” such as neuronal factors of the Oct family including Oct-6 and the transcriptional repressor DREAM. Oct-6 is known to be expressed in brain and testis, to play a role in myelination and to act as an RNA polymerase II distal enhancer (Hofmann et al 2010). DREAM plays a role in nociception in the brain and is broadly expressed in testis (Rivas et al 2004).…”

Section: Resultsmentioning

confidence: 99%

Expression and Sequence Evolution of Aromatase cyp19a1 and Other Sexual Development Genes in East African Cichlid Fishes

Böhne

Heule

Boileau

et al. 2013

Molecular Biology and Evolution

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Sex determination mechanisms are highly variable across teleost fishes and sexual development is often plastic. Nevertheless, downstream factors establishing the two sexes are presumably conserved. Here, we study sequence evolution and gene expression of core genes of sexual development in a prime model system in evolutionary biology, the East African cichlid fishes. Using the available five cichlid genomes, we test for signs of positive selection in 28 genes including duplicates from the teleost whole-genome duplication, and examine the expression of these candidate genes in three cichlid species. We then focus on a particularly striking case, the A- and B-copies of the aromatase cyp19a1, and detect different evolutionary trajectories: cyp19a1A evolved under strong positive selection, whereas cyp19a1B remained conserved at the protein level, yet is subject to regulatory changes at its transcription start sites. Importantly, we find shifts in gene expression in both copies. Cyp19a1 is considered the most conserved ovary-factor in vertebrates, and in all teleosts investigated so far, cyp19a1A and cyp19a1B are expressed in ovaries and the brain, respectively. This is not the case in cichlids, where we find new expression patterns in two derived lineages: the A-copy gained a novel testis-function in the Ectodine lineage, whereas the B-copy is overexpressed in the testis of the speciest-richest cichlid group, the Haplochromini. This suggests that even key factors of sexual development, including the sex steroid pathway, are not conserved in fish, supporting the idea that flexibility in sexual determination and differentiation may be a driving force of speciation.

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Section: Resultsmentioning

confidence: 99%

Expression and Sequence Evolution of Aromatase cyp19a1 and Other Sexual Development Genes in East African Cichlid Fishes

Böhne

Heule

Boileau

et al. 2013

Molecular Biology and Evolution

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“…The conserved peak at −4,8kb corresponds with an estradiol responsive enhancer characterized by Renner and colleagues (Renner et al, 1996). The large conserved region containing the Oct6 gene contains the promoter proximal region at −0.5kb which confers Interferon-β responsiveness and is important for the regulated expression of Oct6 in macrophages (Hofmann et al, 2010). An ultraconserved element flanks the 3′ end of the locus (Figure 1A; arrowhead) at approximately +15kb (Bejerano et al, 2004) and is downstream of the SCE.…”

Section: Resultsmentioning

confidence: 99%

“…Promoter proximal elements mediate interferon and dsRNA responses in fibroblasts, macrophages and possibly Schwann cells through binding of the transcription factor Stat1 (Hofmann et al, 2010). These elements fall within the limits of HSS1.…”

Section: Discussionmentioning

confidence: 99%

Functional Dissection of the Oct6 Schwann Cell Enhancer Reveals an Essential Role for Dimeric Sox10 Binding

Jagalur¹,

Ghazvini²,

Mandemakers³

et al. 2011

Journal of Neuroscience

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The POU domain transcription factor Pou3f1 (Oct6/Scip/Tst1) initiates the transition from ensheathing, promyelinating Schwann cells to myelinating cells. Axonal and other extra-cellular signals regulate Oct6 expression through the Oct6 Schwann cell enhancer (SCE), which is both required and sufficient to drive all aspects of Oct6 expression in Schwann cells. Thus, the Oct6 SCE is pivotal in the gene regulatory network that governs the onset of myelin formation in Schwann cells and provides a link between myelin promoting signalling and activation of a myelin related transcriptional network. In this study we define the relevant cis-acting elements within the SCE and identify the transcription factors that mediate Oct6 regulation. On the basis of phylogenetic comparisons and functional in vivo assays we identify a number of highly conserved core elements within the mouse SCE. We show that core element 1 is absolutely required for full enhancer function and that it contains closely-spaced inverted binding sites for Sox proteins. For the first time in vivo, the dimeric Sox10 binding to this element is shown to be essential for enhancer activity whereas monomeric Sox10 binding is non-functional. As Oct6 and Sox10 synergize to activate the expression of the major myelin-related transcription factor Krox20, we propose that Sox10 dependent activation of Oct6 defines a feed-forward regulatory module that serves to time and amplify the onset of myelination in the peripheral nervous system.

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“…Oct-6 is a class III POU domain protein that has been characterized primarily with respect to its expression in oligodendrocyte precursors, and in developing Schwann cells, where it is required for correctly timed transition to the myelinating state [15,24]. Moreover, it is also expressed in testes, keratinocytes, gastrointestinal epithelium, pancreatic β-cells, and macrophages, this suggesting a more general transcriptional activity for this protein [16,18,25,26,27,28,29,30]. However, the possible role of Oct-6 in cancer has never been investigated.…”

Section: Discussionmentioning

confidence: 99%

The POU-Domain Transcription Factor Oct-6/POU3F1 as a Regulator of Cellular Response to Genotoxic Stress

Fionda

Bona

Kosta

et al. 2019

Cancers

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DNA damage and the generation of reactive oxygen species (ROS) are key mechanisms of apoptotic cell death by commonly used genotoxic drugs. However, the complex cellular response to these pharmacologic agents remains yet to be fully characterized. Several studies have described the role of transcription factor octamer-1 (Oct-1)/Pit-1, Oct-1/2, and Unc-86 shared domain class 2 homeobox 1 (POU2F1) in the regulation of the genes important for cellular response to genotoxic stress. Evaluating the possible involvement of other POU family transcription factors in these pathways, we revealed the inducible expression of Oct-6/POU3F1, a regulator of neural morphogenesis and epidermal differentiation, in cancer cells by genotoxic drugs. The induction of Oct-6 occurs at the transcriptional level via reactive oxygen species (ROS) and ataxia telangiectasia mutated- and Rad3-related (ATR)-dependent mechanisms, but in a p53 independent manner. Moreover, we provide evidence that Oct-6 may play a role in the regulation of cellular response to DNA damaging agents. Indeed, by using the shRNA approach, we demonstrate that in doxorubicin-treated H460 non-small-cell lung carcinoma (NSCLC) cells, Oct-6 depletion leads to a reduced G2-cell cycle arrest and senescence, but also to increased levels of intracellular ROS and DNA damage. In addition, we could identify p21 and catalase as Oct-6 target genes possibly mediating these effects. These results demonstrate that Oct-6 is expressed in cancer cells after genotoxic stress, and suggests its possible role in the control of ROS, DNA damage response (DDR), and senescence.

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

Cited by 15 publications

References 69 publications

Expression and Sequence Evolution of Aromatase cyp19a1 and Other Sexual Development Genes in East African Cichlid Fishes

Expression and Sequence Evolution of Aromatase cyp19a1 and Other Sexual Development Genes in East African Cichlid Fishes

Functional Dissection of the Oct6 Schwann Cell Enhancer Reveals an Essential Role for Dimeric Sox10 Binding

The POU-Domain Transcription Factor Oct-6/POU3F1 as a Regulator of Cellular Response to Genotoxic Stress

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