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首页> 外文期刊>Journal of Molecular Biology >Control elements in the neighboring ATPase gene influence spatiotemporal expression of the human agouti-related protein.
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Control elements in the neighboring ATPase gene influence spatiotemporal expression of the human agouti-related protein.

机译：邻近的ATPase基因中的控制元件会影响人类刺鼠相关蛋白的时空表达。

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摘要

The agouti-related protein (AgRP) is an orexigenic peptide that plays a significant role in the regulation of energy balance. It is expressed in the hypothalamus, the adrenal glands, and the testis, but sequences determining its spatial and temporal expression have not been identified. Using an elaborate in vitro screening approach, we show here that two adjacent enhancers inside the first intron of the neighboring (1.4 kb downstream) ATPase gene (ATP6V0D1) modulate the human AgRP promoter with profound spatiotemporal variation despite their diminutive sizes (221 and 231 nt). In transgenic mice, the proximal enhancer displayed specificity for the testis, tail, and ears, and the distal one for the testis, front feet, bone, heart, muscle, brain, spinal cord, and tongue, while dietary fat and overnight fasting had differential effects on enhancer activities. AgRP in the testis was localized to pachytene spermatocytes and in the tongue to epithelial cells. Comparative sequence analysis showed that the AgRP-ATP6V0D1 intergenic region is two times longer in humans than in mice and that the two enhancers are conserved in the rhesus monkey genome but not in the mouse genome. These data show that spatiotemporal expression of the human AgRP gene is influenced by diversified primate-specific intronic sequences in its neighboring ATP6V0D1 gene.
机译：刺骨相关蛋白（AgRP）是一种致食性肽，在调节能量平衡中起着重要作用。它在下丘脑，肾上腺和睾丸中表达，但尚未确定确定其时空表达的序列。使用精心设计的体外筛选方法，我们在这里显示了邻近（1.4 kb下游）ATPase基因（ATP6V0D1）的第一个内含子内的两个邻近增强子，尽管它们的体积很小（221和231 nt ）。在转基因小鼠中，近端增强子对睾丸，尾巴和耳朵表现出特异性，远端对睾丸，前脚，骨骼，心脏，肌肉，大脑，脊髓和舌头表现出特异性，而饮食脂肪和通宵禁食对增强剂活性的不同作用。睾丸中的AgRP定位于粗线精细胞，而舌头则定位于上皮细胞。比较序列分析表明，人中的AgRP-ATP6V0D1基因间区比小鼠长两倍，并且这两种增强子在恒河猴基因组中保守，而在小鼠基因组中却不保守。这些数据表明，人类AgRP基因的时空表达受到其邻近ATP6V0D1基因中的灵长类特异性内含子序列的影响。

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