The Zfhx3-Mediated Axis Regulates Sleep and Interval Timing in Mice

Balzani, Edoardo; Lassi, Glenda; Maggi, Silvia; Sethi, Siddharth; Parsons, Michael�J.; Simon, Michelle; Nolan, Patrick�M.; Tucci, Valter

Abstract

An AT motif-dependent axis, modulated by the transcription factor Zfhx3, influences the circadian clock in mice. In particular, gain of function of Zfhx3 significantly shortens circadian rhythms and alters the transcriptional activity of an important class of neuropeptides that controls intercellular signaling in the suprachiasmatic nucleus (SCN) of the hypothalamus. The ZFHX3/AT axis revealed an important, largely cell-nonautonomous control of the circadian clock. Here, by studying the recently identified circadian mouse mutant Zfhx3Sci/+, we identify significant effects on sleep homeostasis, a phenomenon that is outside the canonical circadian clock system and that is modulated by the activity of those neuropeptides at a circuit level. We show that the Zfhx3Sci/+ mutation accelerates the circadian clock at both the hourly scale (i.e., advancing circadian rhythms) and the seconds-to-minutes scale (i.e., anticipating behavioral responses) in mice. The in vivo results are accompanied by a significant presence of sleep targets among protein-protein interactions of the Zfhx3Sci/+-dependent network.

Citation

Balzani, E., Lassi, G., Maggi, S., Sethi, S., Parsons, M., Simon, M., Nolan, P., & Tucci, V. (2016). The Zfhx3-Mediated Axis Regulates Sleep and Interval Timing in Mice. Cell Reports, 16(3), 615-621. https://doi.org/10.1016/j.celrep.2016.06.017

• Journal Article Type: Article
• Acceptance Date: May 31, 2016
• Online Publication Date: Jun 30, 2016
• Publication Date: Jul 19, 2016
• Deposit Date: Nov 5, 2019
• Publicly Available Date: Nov 5, 2019
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Electronic ISSN: 2211-1247
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 3
• Pages: 615-621
• DOI: https://doi.org/10.1016/j.celrep.2016.06.017
• Keywords: General Biochemistry, Genetics and Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/3057679
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2211124716307574?via%3Dihub
• Contract Date: Nov 5, 2019