Enhancer gene maps in the human and zebrafish genomes using evolutionary linkage conservation
Enhancer gene maps in the human and zebrafish genomes using evolutionary linkage conservation
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DOI：
10.1093/nar/gkz1199
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发表时间：
2020-03-18
影响因子：
14.9
通讯作者：
Crollius, Hugues Roest
中科院分区：
文献类型：
--
作者：
Clement, Yves;Torbey, Patrick;Crollius, Hugues Roest
基因的时空表达受与转录因子结合的增强子序列控制。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，我们使用进化的方法来建立两个全基因组的预测增强子基因关联的人类和斑马鱼基因组的地图。使用PEGASUS（一种依赖于同线性进化保守性的生物信息学方法）将进化保守序列与其预测的靶基因相关联。对这些图谱的分析揭示了与基因相连的预测增强子的数量与其表达宽度相关。这两个地图的比较确定了数百个推定的脊椎动物祖先的监管关系，我们可以确定，预测增强子基因的距离尺度与基因组的大小，尽管强大的位置保守。这两个图谱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的序列变异的优先次序。
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 enhancergene 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.