Loots G G, Locksley R M, Blankespoor C M, Wang Z E, Miller W, Rubin E M, Frazer K A
Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Science. 2000 Apr 7;288(5463):136-40. doi: 10.1126/science.288.5463.136.
Long-range regulatory elements are difficult to discover experimentally; however, 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.
远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能够识别出它们。为了寻找调控序列，我们检查了约1兆碱基的直系同源人类和小鼠序列，以寻找在至少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显示，它是白细胞介素-4、白细胞介素-13和白细胞介素-5这三个基因的协同调节因子，这三个基因分布在120千碱基上。
