Regulatory roles of conserved intergenic domains in vertebrate Dlx bigene clusters
Regulatory roles of conserved intergenic domains in vertebrate Dlx bigene clusters
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DOI：
10.1101/gr.716103
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发表时间：
2003-04-01
期刊：
影响因子：
7
通讯作者：
Ekker, M
中科院分区：
文献类型：
--
作者：
Ghanem, N;Jarinova, O;Ekker, M
脊椎动物的D1 x同源盒基因通常在不同的染色体上排列为三个双基因簇。D1 x1/D1 x2、D1 x5/D1 x6和D1 x3/D1 x7簇可能起源于祖先D1 x基因对的重复。在来自不同簇的基因之间经常观察到表达的重叠。为了确定重叠是否是旁系同源簇之间增强子序列保守的结果，我们比较了来自人类、小鼠、斑马鱼和两种河豚鱼Spheroides nephelus和红鳍东方鲀的D1 x1/2和D1 x5/D1 x6基因间区域。所有五种脊椎动物之间的保守性仅限于四个序列，两个在D1 x1/D1 x2和两个在D1 x5/D1 x6。这些非编码序列在几百个碱基对上有超过75%的相同性，即使在遥远的脊椎动物中也是如此。然而，当相互比较时，四个基因间序列显示出有限得多的相似性。当在转基因动物中测试时，每个基因间序列充当增强子。其中三个是活跃在前脑重叠的模式，尽管他们有限的序列相似性。旁系同源的基因间区域之间的序列相似性和高程度的序列保守性的orthopathic增强子建议的D1 x基因间区域的快速分歧，在脊索动物/脊椎动物进化的早期，随后固定的顺式作用调控元件。
D1x homeobox genes of vertebrates are generally arranged as three bigene clusters on distinct chromosomes. The D1x1/D1x2, D1x5/D1x6, and D1x3/D1x7 clusters likely originate from duplications of an ancestral D1x gene pair. Overlaps in expression are often observed between genes from the different clusters. To determine if the overlaps are a result of the conservation of enhancer sequences between paralogous clusters, we compared the D1x1/2 and the D1x5/D1x6 intergenic regions from human, mouse, zebrafish, and from two pufferfish, Spheroides nephelus and Takifugu rubripes. Conservation between all five vertebrates is limited to four sequences, two in D1x1/D1x2 and two in D1x5/D1x6. These noncoding sequences are >75% identical over a few hundred base pairs, even in distant vertebrates. However, when compared to each other, the four intergenic sequences show a much more limited similarity. Each intergenic sequence acts as an enhancer when tested in transgenic animals. Three of them are active in the forebrain with overlapping patterns despite their limited sequence similarity. The lack of sequence similarity between paralogous intergenic regions and the high degree of sequence conservation of orthologous enhancers suggest a rapid divergence of D1x intergenic regions early in chordate/vertebrate evolution followed by fixation of cis-acting regulatory elements.