Cyclin C regulated oxidative stress responsive transcriptome in mus musculus embryonic fibroblasts

David C. Stieg, Kai Ti Chang, Katrina F. Cooper, Randy Strich

    Research output: Contribution to journalArticlepeer-review

    5 Scopus citations

    Abstract

    The transcriptional changes that occur in response to oxidative stress help direct the decision to maintain cell viability or enter a cell death pathway. Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively stressed Mus musculus embryonic fibroblasts. We observed a similar number (2000) of genes up or downregulated in oxidatively stressed cells. Induced genes include cellular repair/survival factors while repressed loci were generally involved in proliferation or differentiation. Depleting cyclin C in unstressed cells produced an approximately equal number of genes (2400) that were repressed by, or whose transcription required, cyclin C. Consistent with the possibility that cyclin C nuclear release contributes to transcriptional remodeling in response to oxidative stress, we found that 37% cyclin C-dependent genes were downregulated following stress. Moreover, 20% of cyclin C- repressed genes were induced in response to stress. These findings are consistent with a model that cyclin C relocalization to the cytoplasm, and corresponding inactivation of Cdk8, represents a regulatory mechanism to repress and stimulate transcription of stress-responsive genes.

    Original languageEnglish (US)
    Pages (from-to)1901-1908
    Number of pages8
    JournalG3: Genes, Genomes, Genetics
    Volume9
    Issue number6
    DOIs
    StatePublished - 2019

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Genetics
    • Genetics(clinical)

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