The circadian rhythm is regulated by a set of clock transcription factors whose expression and activity depend on a number of interdependent, oscillating post-translational modifications. Kim et al. now provide evidence that the key clock transcription factor PERIOD (dPER) in Drosophila melanogaster is O-GlcNAcylated and that this modification affects the circadian clock in flies. The authors overexpressed dPER and the O-GlcNAc transferase (OGT) in a Drosophila cell line and observed that dPER is modified by O-GlcNAc. In vivo modulation of O-GlcNAcylation, by either knocking down or overexpressing OGT in neurons responsible for the Drosophila clock, resulted in flies with altered circadian activity. To validate in vivo that O-GlcNAcylated dPER is present and controls the circadian rhythm, the authors examined the O-GlcNAcylation of dPER during a 24-h cycle and observed an increase in the modification during the dark phase that could not be attributed to changes in OGT activity. Knockdown or overexpression of ogt in flies resulted in decreased or increased amounts of total dPER, respectively, which correlated with advanced or delayed nuclear localization timing. As a result, the authors concluded that O-GlcNAcylation of dPER occurs shortly after its synthesis and leads to increased protein stability and delayed nuclear entry via cytoplasmic retention. These results highlight a new role for O-GlcNAcylation in pacing the circadian rhythm.
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20 June 2012
In the version of this article initially published, the doi for the article referred to in the highlight entitled "O-GlcNAc in the dark" is incorrect. The correct doi is 10.1101/gad.182378.111. The errors have been corrected in the HTML and PDF versions of the article.
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Chalkiadaki, A. O-GlcNAc in the dark. Nat Chem Biol 8, 320 (2012). https://doi.org/10.1038/nchembio.928
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DOI: https://doi.org/10.1038/nchembio.928
