Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons
Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons
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DOI：
10.1126/science.288.5463.136
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发表时间：
2000-04-07
期刊：
影响因子：
56.9
通讯作者：
Frazer, KA
中科院分区：
文献类型：
--
作者：
Loots, GG;Locksley, RM;Frazer, KA
长距离调控元件很难通过实验发现;然而，它们在哺乳动物中往往是保守的，这表明跨物种序列比较应该识别它们。为了寻找调控序列，我们检测了大约100万碱基的人类和小鼠的同源序列，以寻找至少100个碱基对上具有大于或等于70%同一性的保守非编码元件。发现了90个符合这些标准的非编码序列，对其中15个元件的分析发现，约70%在哺乳动物中是保守的。对酵母人工染色体转基因小鼠中最大元件的表征表明，它是分布在120种酶上的三种基因（白细胞介素-4、白细胞介素-13和白细胞介素-5）的协调调节因子。
Long-range regulatory elements are difficult to discover experimentally; how-ever, they tend to be conserved among mammals, suggesting that cross-species sequence comparisons should identify them. To search for regulatory sequences, we examined about 1 megabase of orthologous human and mouse sequences for conserved noncoding elements with greater than or equal to 70% identity over at Least 100 base pairs. Ninety noncoding sequences meeting these criteria were discovered, and the analysis of 15 of these elements found that about 70% were conserved across mammals. Characterization of the Largest element in yeast artificial chromosome transgenic mice revealed it to be a coordinate regulator of three genes, interleukin-4, interleukin-13, and interleukin-5, spread over 120 kilobases.