The transcriptional repressor Rev-erbα regulates circadian expression of the astrocyte Fabp7 mRNA.

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 . We confirmed that Rev-erbα binds to the promoter in multiple brain areas, including hippocampus, hypothalamus, and VTA, and showed that gene expression is upregulated in knock-out mice. Compared to mRNA levels, and mRNA were unaffected by depletion in hippocampus, suggesting that these effects are specific to . To determine whether these effects of depletion occur broadly throughout the brain, we also evaluated mRNA expression levels in multiple brain areas, including cerebellum, cortex, hypothalamus, striatum, and VTA in knock-out mice. While small but significant changes in mRNA expression exist in some of these areas, the magnitude of these effects are minimal to that of mRNA expression, which was over 6-fold across all brain regions. These studies suggest that Rev-erbα is a transcriptional repressor of gene expression throughout mammalian brain.