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Homologous DNA sequences and cellular factors are implicated in the control of glucagon and insulin gene expression.

机译:同源DNA序列和细胞因子与胰高血糖素和胰岛素基因表达的控制有关。

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The glucagon gene is specifically expressed in the alpha cells of pancreatic islets. The promoter of the glucagon gene is responsible for this specificity. Within the promoter, the upstream promoter element G1 is critical to restrict expression to the alpha cells. We define here a composite DNA control element, G4, localized upstream of G1 between nucleotides -100 and -140 which functions as an islet-specific activator in both glucagon- and insulin-producing cells but not in nonislet cells. G4 contains at least three protein binding sites. The most proximal site, E2, is highly homologous to the E1, SMS-UE, and B elements of the rat insulin I, somastatin, and elastase I genes, respectively, and interacts with a pancreas-specific complex; the distal site, E3, represents an E box which is identical to the E boxes of the rat insulin I and II genes and binds to a complex similar or identical to IEF1 which has been implicated in the tissue-specific control of insulin gene expression. These two sites necessitate a third element, the intervening sequence, to activate transcription. We conclude that the first 140 bp of the glucagon gene promoter contains at least two DNA control elements responsible for pancreatic alpha-cell-specific expression: G4, an islet cell-specific element sharing common binding sites with the insulin gene, and G1, which restricts glucagon gene expression to the alpha cells. This double control of specificity might have relevance during islet cell differentiation.
机译:胰高血糖素基因在胰岛的α细胞中特异性表达。胰高血糖素基因的启动子负责这种特异性。在启动子内,上游启动子元件G1对于限制表达至α细胞至关重要。我们在这里定义了一个复合DNA控制元件G4,位于G1上游的核苷酸-100和-140之间,在胰高血糖素和胰岛素生产细胞中均充当胰岛特异性活化剂,但在非胰岛细胞中则不起作用。 G4包含至少三个蛋白质结合位点。最接近的位点E2分别与大鼠胰岛素I,生长抑素和弹性蛋白酶I基因的E1,SMS-UE和B元素高度同源,并且与胰腺特异性复合物相互作用。远端位点E3代表一个E盒,该E盒与大鼠胰岛素I和II基因的E盒相同,并与与IEF1类似或相同的复合物结合,该复合物与胰岛素基因表达的组织特异性控制有关。这两个位点需要第三个元件,即插入序列来激活转录。我们得出的结论是,胰高血糖素基因启动子的前140 bp包含至少两个负责胰腺α细胞特异性表达的DNA控制元件:G4,与胰岛素基因共享共同结合位点的胰岛细胞特异性元件,以及G1,限制胰高血糖素基因表达到α细胞。在胰岛细胞分化过程中,特异性的双重控制可能具有相关性。

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