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J Biol Rhythms. 2018 Apr;33(2):166-178. doi: 10.1177/0748730418761236.

Regulation of the Neuroligin-1 Gene by Clock Transcription Factors.

Author information

1
Department of Psychiatry, Université de Montréal, Montreal, Quebec, Canada.
2
Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada.
3
Department of Neuroscience, Université de Montréal, Montreal, Quebec, Canada.
4
Department of Pharmacology and Physiology, Université de Montréal, Montreal, Quebec, Canada.
5
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
6
Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Abstract

NEUROLIGIN-1 (NLGN1) is a postsynaptic adhesion molecule involved in the regulation of glutamatergic transmission. It has been associated with several features of sleep and psychiatric disorders. Our previous work suggested that transcription of the Nlgn1 gene could be regulated by the transcription factors CLOCK and BMAL1 because they bind to the Nlgn1 gene promoter in vivo. However, whether CLOCK/BMAL1 can directly activate Nlgn1 transcription is not yet known. We thus aimed to verify whether CLOCK/BMAL1, as well as their homologs NPAS2 and BMAL2, can activate transcription via the Nlgn1 promoter by using luciferase assays in COS-7 cells. We also investigated how Nlgn1 expression was affected in Clock mutant mice. Our results show transcriptional activation in vitro mediated by CLOCK/BMAL1 and by combinations with their homologs NPAS2 and BMAL2. Moreover, CLOCK/BMAL1 activation via the Nlgn1 gene fragment was repressed by GSK3β. In vivo, Nlgn1 mRNA expression was significantly modified in the forebrain of Clock mutant mice in a transcript variant-dependent manner. However, no significant change in NLGN1 protein level was observed in Clock mutant mice. These findings will increase knowledge about the transcriptional regulation of Nlgn1 and the relationship between circadian rhythms, mental health, and sleep.

KEYWORDS:

E-boxes; cell adhesion molecules; circadian timing system; clock proteins; gene expression; luciferase assay; mice; transcription

PMID:
29671709
DOI:
10.1177/0748730418761236
[Indexed for MEDLINE]

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