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Egr1 involvement in evening gene regulation by melatonin
J M Fustin1, H Dardente, G C Wagner
1Aberdeen University, School of Biological Sciences, Department of Zoology, Tillydrone Avenue, Aberdeen, AB242TZ, Scotland, UK.
Summary
Melatonin, a key hormone for seasonal responses, influences gene expression in the pituitary pars tuberalis (PT). This study reveals that the immediate early gene EGR1 mediates melatonin
Area of Science:
- Endocrinology
- Molecular Biology
- Chronobiology
Background:
- Seasonal adaptations in mammals are regulated by melatonin, a hormone produced by the pineal gland.
- The pars tuberalis (PT) of the anterior pituitary is a primary target tissue for melatonin, mediating crucial endocrine functions.
- Melatonin acutely alters the expression of specific genes in the PT, including positive regulators like cryptochrome-1 (cry1) and negative regulators like the melatonin receptor 1 (mt1).
Purpose of the Study:
- To elucidate the molecular pathways responsible for the immediate effects of melatonin on gene expression in the PT.
- To investigate the role of cAMP signaling and the immediate early gene EGR1 in mediating melatonin's actions.
- To characterize the transcriptional regulation of cry1 and mt1 genes by melatonin in the PT.
Main Methods:
- In vitro studies using PT cell cultures to assess the impact of melatonin and cAMP signaling on gene expression.
- Analysis of nuclear extracts from sheep PT tissue following melatonin or saline administration to identify regulatory elements.
- Luciferase reporter assays to confirm the functionality of identified EGR1 response elements (EGR1-REs) in the promoter regions of cry1 and mt1.
Main Results:
- cAMP signaling directly modulates mt1 expression but not cry1 expression in the PT.
- The EGR1 response element (EGR1-RE) was identified as a key mediator of acute melatonin-dependent gene regulation in the ovine PT.
- Putative EGR1-REs in the cry1 and mt1 promoters were confirmed to be functional.
- Melatonin suppresses Egr1 expression in PT cells, and Egr1 exhibits a daily rhythm with its lowest point in the early night.
Conclusions:
- Melatonin's evening actions on gene expression in the PT involve the regulation of EGR1.
- The identified EGR1-REs in the cry1 and mt1 genes are critical for mediating melatonin's effects on their transcription.
- These findings elucidate a novel mechanism by which melatonin influences gene expression in a key neuroendocrine tissue, contributing to seasonal adaptation.
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