4.8 Article

SOX2-Dependent Transcription in Clock Neurons Promotes the Robustness of the Central Circadian Pacemaker

Journal

CELL REPORTS
Volume 26, Issue 12, Pages 3191-+

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2019.02.068

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Funding

  1. Canadian Institutes of Health Research (CIHR)
  2. Natural Sciences and Engineering Research Council (NSERC) of Canada
  3. NSERC Tier II Canada Research Chair in Molecular Genetics of Biological Clocks
  4. NSERC
  5. Canadian Foundation for Innovation

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Clock neurons within the mammalian suprachiasmatic nuclei (SCN) encode circadian time using interlocked transcription-translation feedback loops (TTFLs) that drive rhythmic gene expression. However, the contributions of other transcription factors outside of the circadian TTFLs to the functionality of the SCN remain obscure. Here, we report that the stem and progenitor cell transcription factor, sex-determining region Y-box 2 (SOX2), is expressed in adult SCN neurons and positively regulates transcription of the core clock gene, Period2. Mice lacking SOX2 selectively in SCN neurons display imprecise, poorly consolidated behavioral rhythms that do not entrain efficiently to environmental light cycles and that are highly susceptible to constant light-induced arrhythmicity. RNA sequencing revealed that Sox2 deficiency alters the SCN transcriptome, reducing the expression of core clock genes and neuropeptide-receptor systems. By defining the transcriptional landscape within SCN neurons, SOX2 enables the generation of robust, entrainable circadian rhythms that accurately reflect environmental time.

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