The transcriptional repressor Rev-erbα regulates circadian expression of the astrocyte Fabp7 mRNA.
The transcriptional repressor Rev-erbα regulates circadian expression of the astrocyte Fabp7 mRNA.
复制标题
转录抑制因子 Rev-erbα 调节星形胶质细胞 Fabp7 mRNA 的昼夜节律表达。
DOI：
10.1016/j.crneur.2021.100009
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Gerstner,JasonR
中科院分区：
文献类型：
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作者：
Vanderheyden,WilliamM;Fang,Bin;Flores,CarlosC;Jager,Jennifer;Gerstner,JasonR
星形胶质细胞脑型脂肪酸结合蛋白（Fabp 7）昼夜节律基因表达在整个哺乳动物大脑中同步于相同的时间相位。促进这种协调表达的细胞和分子机制尚未完全了解，但可能涉及核受体Rev-erbα（NR 1D 1），一种转录抑制因子。我们对腹侧被盖区（VTA）进行了ChIP-seq，并确定了Rev-erbα的基因靶点，包括Fabp 7。我们证实了Rev-erbα在多个脑区与Fabp 7启动子结合，包括海马、下丘脑和VTA，并表明Fabp 7基因表达在Rev-erb α敲除小鼠中上调。与Fabp 7 mRNA水平相比，海马中Fabp 3和Fabp 5 mRNA不受Rev-erb α耗竭的影响，表明这些影响是Fabp 7特异性的。为了确定Rev-erb α缺失的这些效应是否广泛地发生在整个大脑中，我们还评估了多个脑区域中FabpmRNA的表达水平，包括Rev-erb α敲除小鼠的小脑、皮质、下丘脑、纹状体和VTA。虽然在这些区域中的一些区域中存在Fabp 5 mRNA表达的小但显著的变化，但这些影响的幅度与Fabp 7 mRNA表达的影响相比是最小的，Fabp 7 mRNA表达在所有脑区中超过6倍。这些研究表明Rev-erbα是哺乳动物脑内Fabp 7基因表达的转录抑制因子。
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, includingFabp7. We confirmed that Rev-erbα binds to theFabp7promoter in multiple brain areas, including hippocampus, hypothalamus, and VTA, and showed thatFabp7gene expression is upregulated inRev-erbαknock-out mice. Compared toFabp7mRNA levels,Fabp3andFabp5mRNA were unaffected byRev-erbαdepletion in hippocampus, suggesting that these effects are specific toFabp7. To determine whether these effects ofRev-erbαdepletion occur broadly throughout the brain, we also evaluatedFabpmRNA expression levels in multiple brain areas, including cerebellum, cortex, hypothalamus, striatum, and VTA inRev-erbαknock-out mice. While small but significant changes inFabp5mRNA expression exist in some of these areas, the magnitude of these effects are minimal to that ofFabp7mRNA expression, which was over 6-fold across all brain regions. These studies suggest that Rev-erbα is a transcriptional repressor ofFabp7gene expression throughout mammalian brain.