Regulation of theNeuroligin-1Gene by Clock Transcription Factors
| Autor: | Nicolas Cermakian, Erika Bélanger-Nelson, Emma K. O’Callaghan, Julien Dufort-Gervais, Pierre-Gabriel Roy, Lydia Hannou, Maria Neus Ballester Roig, Valérie Mongrain, Jean-Martin Beaulieu |
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| Rok vydání: | 2018 |
| Předmět: |
Transcriptional Activation
0301 basic medicine Physiology Cell Adhesion Molecules Neuronal Mutant CLOCK Proteins Biology Mice 03 medical and health sciences Transcription (biology) Physiology (medical) Chlorocebus aethiops Gene expression Transcriptional regulation Animals Promoter Regions Genetic Transcription factor NPAS2 ARNTL Transcription Factors Promoter Circadian Rhythm 3. Good health Cell biology 030104 developmental biology Gene Expression Regulation COS Cells Transcription Factors |
| Zdroj: | Journal of Biological Rhythms. 33:166-178 |
| ISSN: | 1552-4531 0748-7304 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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