Evolutionary conservation of glucose-dependent insulinotropic polypeptide (GIP) gene regulation and the enteroinsular axis.
Evolutionary conservation of glucose-dependent insulinotropic polypeptide (GIP) gene regulation and the enteroinsular axis.
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DOI：
10.1016/j.regpep.2010.05.007
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发表时间：
2010-09-24
影响因子：
--
通讯作者：
Wolfe, M. Michael
中科院分区：
文献类型：
--
作者：
Musson, Michelle C.;Jepeal, Lisa I.;Sharifnia, Torfay;Wolfe, M. Michael
葡萄糖依赖性胰岛素多肽（GIP）是肠岛轴的重要组成部分，是胰岛素分泌的有效刺激物，具有维持营养效率的功能。虽然在哺乳动物中有很好的特征，但很少有人知道GIP在达尼奥河中的转录调控（Dr .）。我们之前证明了DrGIP在肠道和胰腺中表达，因此我们克隆了Dr启动子来比较Dr和哺乳动物中GIP的转录调控。尽管高度保守的哺乳动物启动子与DrGIP启动子之间没有明显的同源性，但1072 bp的DrGIP启动子在哺乳动物细胞系中具有组织特异性表达。对DrGIP启动子的缺失分析确定了两个区域，当缺失时，转录分别减少了75%和95%。上游区域的突变分析表明与Nkx结合位点有关，尽管我们无法确定与该位点结合的因子。发现下游区域的cis元件是GATA结合位点。最后，过表达和shRNA实验发现PAX4是DrGIP表达的潜在抑制因子。这些发现提供了证据，尽管确定了物种特异性转录调控因子，并且在丹尼奥河鼠和哺乳动物之间的GIP表达模式存在差异，但似乎存在中等程度的调控守恒。
Glucose-dependent insulinotropic polypeptide (GIP), an important component of the enteroinsular axis, is a potent stimulator of insulin secretion, functioning to maintain nutrient efficiency. Although well-characterized in mammals, little is known regarding GIP transcriptional regulation in Danio rerio (Dr). We previously demonstrated that DrGIP is expressed in the intestine and the pancreas, and we therefore cloned the Dr promoter to compare GIP transcriptional regulation in Dr and mammals. Although no significant homology was indentified between the highly conserved mammalian promoter and the DrGIP promoter, 1072-bp of the DrGIP promoter conferred tissue-specific expression in mammalian cell lines. Deletional analysis of the DrGIP promoter identified two regions that, when deleted, reduced transcription by 75% and 95%, respectively. Mutational analysis of the upstream region suggested involvement of an Nkx binding site, although we were unable to identify the factor binding to this site. The cis element in the downstream region was found to be a GATA binding site. Lastly, overexpression and shRNA experiments identified PAX4 as a potential repressor of DrGIP expression. These findings provide evidence that despite the identification of species-specific transcriptional regulators and differences in GIP expression patterns between Danio rerio and mammals, a moderate degree of regulatory conservation appears to exist.
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影响因子：
4.4
作者：
Inoue, H;Rudnick, A;Permutt, MA
通讯作者：
Permutt, MA
影响因子：
--
作者：
Jepeal, LI;Boylan, MO;Wolfe, MM
通讯作者：
Wolfe, MM
影响因子：
4.1
作者：
Jepeal, Lisa I.;Boylan, Michael O.;Wolfe, M. Michael
通讯作者：
Wolfe, M. Michael
DOI：
10.1152/ajpgi.2001.280.1.g58
发表时间：
2001-01-01
影响因子：
4.5
作者：
Fang, RX;Olds, LC;Sibley, E
通讯作者：
Sibley, E
影响因子：
4.8
作者：
CHEN, CY;SCHWARTZ, RJ
通讯作者：
SCHWARTZ, RJ