Control elements in the neighboring ATPase gene influence spatiotemporal expression of the human agouti-related protein.
Control elements in the neighboring ATPase gene influence spatiotemporal expression of the human agouti-related protein.
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DOI：
10.1016/j.jmb.2009.03.017
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发表时间：
2009-05-01
影响因子：
5.6
通讯作者：
Argyropoulos, George
中科院分区：
文献类型：
--
作者：
Llnytska, Olha;Sozen, Mehmet A.;Dauterive, Rachel;Argyropoulos, George
AgRP是一种在能量平衡调节中起重要作用的促食欲肽。它在下丘脑、肾上腺和睾丸中表达，但决定其空间和时间表达的序列尚未确定。使用一个精心设计的体外筛选方法，我们在这里显示，两个相邻的增强子内的第一个内含子的相邻（1.4 kb下游）ATP酶基因（ATP 6V 0 D1）调节人类AgRP启动子具有深刻的时空变化，尽管他们的小尺寸（221 nt和231 nt）。在转基因小鼠中，近端增强子对睾丸、尾巴和耳朵具有特异性，远端增强子对睾丸、前脚、骨骼、心脏、肌肉、大脑、脊髓和舌头具有特异性，而膳食脂肪和过夜禁食对增强子活性具有不同的影响。AgRP在睾丸中定位于粗线期精母细胞，在舌中定位于上皮细胞。比较序列分析表明，AgRP-ATP 6V 0 D1基因间区域在人类中比在小鼠中长两倍，并且这两个增强子在恒河猴中是保守的，但在小鼠基因组中不是。这些数据表明，时空表达的人AgRP基因的影响，在其相邻的ATP 6V 0 D1基因的多样性灵长类动物特异性内含子序列。
The Agouti Related Protein (AgRP) is an orexigenic peptide that plays a significant role in energy balance regulation. 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 nt 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 but not 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.
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影响因子：
2.5
作者：
Fukami, H;Bradley, RM
通讯作者：
Bradley, RM
影响因子：
3.5
作者：
Faurholm, Bjarne;Cochrane, Shaun;Katz, Arieh A.
通讯作者：
Katz, Arieh A.
影响因子：
5.8
作者：
Argyropoulos, G;Rankinen, T;Bouchard, C
通讯作者：
Bouchard, C
影响因子：
25
作者：
Gropp, E;Shanabrough, M;Brüning, JC
通讯作者：
Brüning, JC
DOI：
10.1006/bbrc.2000.4003
发表时间：
2000-12-20
影响因子：
3.1
作者：
Agarwal, AK;White, PC
通讯作者：
White, PC