1. The transcriptional repressor Rev-erbα regulates circadian expression of the astrocyte Fabp7 mRNA
- Author
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Vanderheyden, William M., Fang, Bin, Flores, Carlos C., Jager, Jennifer, and Gerstner, Jason R.
- Abstract
The astrocyte brain-type fatty-acid binding protein (Fabp7) circadian gene expression is synchronized in the same temporal phase throughout mammalian brain. Cellular and molecular mechanisms that contribute to this coordinated expression are not completely understood, but likely involve the nuclear receptor Rev-erbα (NR1D1), a transcriptional repressor. We performed ChIP-seq on ventral tegmental area (VTA) and identified gene targets of Rev-erbα, including Fabp7. We confirmed that Rev-erbα binds to the Fabp7promoter in multiple brain areas, including hippocampus, hypothalamus, and VTA, and showed that Fabp7gene expression is upregulated in Rev-erbαknock-out mice. Compared to Fabp7mRNA levels, Fabp3and Fabp5mRNA were unaffected by Rev-erbαdepletion in hippocampus, suggesting that these effects are specific to Fabp7. To determine whether these effects of Rev-erbαdepletion occur broadly throughout the brain, we also evaluated FabpmRNA expression levels in multiple brain areas, including cerebellum, cortex, hypothalamus, striatum, and VTA in Rev-erbαknock-out mice. While small but significant changes in Fabp5mRNA expression exist in some of these areas, the magnitude of these effects are minimal to that of Fabp7mRNA expression, which was over 6-fold across all brain regions. These studies suggest that Rev-erbα is a transcriptional repressor of Fabp7gene expression throughout mammalian brain.
- Published
- 2021
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