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Cell Rep. 2019 Mar 19;26(12):3191-3202.e8. doi: 10.1016/j.celrep.2019.02.068.

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

Author information

1
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada; Department of Cell & Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
2
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
3
Department of Chemistry, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan, ROC.
4
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada; Department of Ecology & Evolutionary Biology, University of Toronto, Toronto, ON M5S 3B2, Canada.
5
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada; Department of Cell & Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada. Electronic address: haiying.cheng@utoronto.ca.

Abstract

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.

KEYWORDS:

PERIOD2; RNA sequencing; SOX2; behavior; circadian rhythms; stem cell transcription factor; suprachiasmatic nucleus; transcription

PMID:
30893593
DOI:
10.1016/j.celrep.2019.02.068
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