The spatiotemporal expression of genes is controlled by enhancer sequences that bind transcription factors. Identifying the target genes of enhancers remains difficult because enhancers regulate gene expression over long genomic distances. To address this, we used an evolutionary approach to build two genome-wide maps of predicted enhancer-gene associations in the human and zebrafish genomes. Evolutionary conserved sequences were linked to their predicted target genes using PEGASUS, a bioinformatics method that relies on evolutionary conservation of synteny. The analysis of these maps revealed that the number of predicted enhancers linked to a gene correlate with its expression breadth. Comparison of both maps identified hundreds of putative vertebrate ancestral regulatory relationships from which we could determine that predicted enhancer-gene distances scale with genome size despite strong positional conservation. The two maps represent a resource for further studies, including the prioritization of sequence variants in whole genome sequence of patients affected by genetic diseases.

中文翻译：

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使用进化连锁保护的人类和斑马鱼基因组中的增强子基因图谱。

基因的时空表达由结合转录因子的增强子序列控制。识别增强子的靶基因仍然很困难，因为增强子在很长的基因组距离上调节基因表达。为了解决这个问题，我们使用进化方法构建了人类和斑马鱼基因组中预测的增强子基因关联的两个全基因组图谱。使用 PEGASUS 将进化保守序列与其预测的靶基因相关联，PEGASUS 是一种依赖同线进化守恒的生物信息学方法。对这些图谱的分析表明，与基因相关的预测增强子的数量与其表达广度相关。两个地图的比较确定了数百个假定的脊椎动物祖先调控关系，我们可以从中确定预测的增强子基因距离与基因组大小成比例，尽管有很强的位置保守性。这两张地图代表了进一步研究的资源，包括受遗传疾病影响的患者的全基因组序列中序列变异的优先排序。