Sun Hong, Skogerbø Geir, Wang Zhen, Liu Wei, Li Yixue
Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
PLoS One. 2008;3(11):e3727. doi: 10.1371/journal.pone.0003727. Epub 2008 Nov 14.
Large numbers of sequence elements have been identified to be highly conserved among vertebrate genomes. These highly conserved elements (HCEs) are often located in or around genes that are involved in transcription regulation and early development. They have been shown to be involved in cis-regulatory activities through both in vivo and additional computational studies. We have investigated the structural relationships between such elements and genes in six vertebrate genomes human, mouse, rat, chicken, zebrafish and tetraodon and detected several thousand cases of conserved HCE-gene associations, and also cases of HCEs with no common target genes. A few examples underscore the potential significance of our findings about several individual genes. We found that the conserved association between HCE/HCEs and gene/genes are not restricted to elements by their absolute distance on the genome. Notably, long-range associations were identified and the molecular functions of the associated genes do not show any particular overrepresentation of the functional categories previously reported. HCEs in close proximity are found to be linked with different set of gene/genes. The results reflect the highly complex correlation between HCEs and their putative target genes.
大量的序列元件已被确定在脊椎动物基因组中高度保守。这些高度保守元件（HCEs）通常位于参与转录调控和早期发育的基因内部或周围。通过体内实验和其他计算研究表明，它们参与顺式调控活动。我们研究了人类、小鼠、大鼠、鸡、斑马鱼和河豚六种脊椎动物基因组中此类元件与基因之间的结构关系，检测到数千例保守的HCE-基因关联情况，以及一些没有共同靶基因的HCEs情况。几个例子强调了我们关于几个单个基因的发现的潜在重要性。我们发现HCE与基因之间的保守关联并不局限于基因组上它们的绝对距离所决定的元件。值得注意的是，我们识别出了长程关联，并且相关基因的分子功能并未显示出先前报道的功能类别有任何特别的过度富集。发现紧邻的HCEs与不同的基因集相关联。结果反映了HCEs与其假定靶基因之间高度复杂的相关性。
