Conservation of regulatory elements between two species of Drosophila
Conservation of regulatory elements between two species of Drosophila
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DOI：
10.1186/1471-2105-4-57
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发表时间：
2003-11-20
影响因子：
3
通讯作者：
Siggia, ED
中科院分区：
文献类型：
--
作者：
Emberly, E;Rajewsky, N;Siggia, ED
背景：后基因组时代的重要目标之一是确定给定生物体基因组的非编码 DNA 内的调控元件。功能性顺式调节模块的识别已被证明是困难的，因为成分因子结合位点很小并且控制其排列的规则知之甚少。然而，适当分化的物种的基因组有助于基于普遍接受的假设（即保守的基因组序列块可能具有功能）来预测调控元件。为了判断通过序列保守进行预过滤的策略的有效性，重要的是要知道相反的假设在多大程度上成立，即两个物种共有的功能元件将落入这些保守的块内。最近完成的第二个果蝇物种的序列提供了一个机会来测试这一假设，即多细胞生物中实验研究得最好的调控网络之一，即果蝇胚胎的身体模式。结果：我们发现 50%-70% 的已知结合位点位于保守序列块中，但这些百分比并没有比偶然预期的大大丰富。最后，基于结合位点簇在两个物种中对调节模块进行的计算全基因组搜索表明，调节网络的核心基因得到了一致的恢复。结论：我们的结果表明，这些“核心模块”的结合位点仍然聚集在一起，而不一定驻留在保守的块中。这是关于基因组中调控信息如何编码以及模块如何进化的重要线索。
Background: One of the important goals in the post-genomic era is to determine the regulatory elements within the non-coding DNA of a given organism's genome. The identification of functional cis-regulatory modules has proven difficult since the component factor binding sites are small and the rules governing their arrangement are poorly understood. However, the genomes of suitably diverged species help to predict regulatory elements based on the generally accepted assumption that conserved blocks of genomic sequence are likely to be functional. To judge the efficacy of strategies that prefilter by sequence conservation it is important to know to what extent the converse assumption holds, namely that functional elements common to both species will fall within these conserved blocks. The recently completed sequence of a second Drosophila species provides an opportunity to test this assumption for one of the experimentally best studied regulatory networks in multicellular organisms, the body patterning of the fly embryo.Results: We find that 50%-70% of known binding sites reside in conserved sequence blocks, but these percentages are not greatly enriched over what is expected by chance. Finally, a computational genome-wide search in both species for regulatory modules based on clusters of binding sites suggests that genes central to the regulatory network are consistently recovered.Conclusions: Our results indicate that binding sites remain clustered for these "core modules" while not necessarily residing in conserved blocks. This is an important clue as to how regulatory information is encoded in the genome and how modules evolve.