Conservation in first introns is positively associated with the number of exons within genes and the presence of regulatory epigenetic signals.
Conservation in first introns is positively associated with the number of exons within genes and the presence of regulatory epigenetic signals.
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DOI：
10.1186/1471-2164-15-526
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发表时间：
2014-06-26
期刊：
影响因子：
4.4
通讯作者：
Choi SS
中科院分区：
文献类型：
--
作者：
Park SG;Hannenhalli S;Choi SS
高等真核生物的基因组具有令人惊讶的长第一内含子，并且在某些情况下，第一内含子已被证明相对于其他内含子具有更高的保守性。然而，对第一个内含子中保守区域的功能相关性知之甚少。利用最近的 ENCODE 数据，我们评估了人类基因第一个内含子中保守区域的潜在调控作用。我们首先表明，相对于其他下游内含子，第一个内含子富集了高度保守的序列块。我们还发现，第一个内含子富集了几个指示活性调节区域的染色质标记，并且这种调节标记的富集与第一个内含子中保守块的富集相关；第一个内含子中保护和调控标记的丰富性不能完全用某些标记偏向内含子 5' 端的一般性（尽管是可变的）来解释。有趣的是，基因第一个内含子中主动调节染色质标记的保守性和比例与基因中外显子的数量呈正相关，但这种相关性在第二个内含子中显着减弱，并且在第二个内含子之外可以忽略不计。第一个内含子保守性也与该基因在多种人体组织中的表达水平呈正相关。最后，基因分析显示，相对于同一基因的其他内含子中的保守区域，第一个内含子的保守区域中的活性染色质标记显着富集。综上所述，我们的分析强烈表明，第一个内含子在纯化选择下富集了活性转录调控信号。本文的在线版本 (doi:10.1186/1471-2164-15-526) 包含补充材料，可供授权用户使用。
Genomes of higher eukaryotes have surprisingly long first introns and in some cases, the first introns have been shown to have higher conservation relative to other introns. However, the functional relevance of conserved regions in the first introns is poorly understood. Leveraging the recent ENCODE data, here we assess potential regulatory roles of conserved regions in the first intron of human genes. We first show that relative to other downstream introns, the first introns are enriched for blocks of highly conserved sequences. We also found that the first introns are enriched for several chromatin marks indicative of active regulatory regions and this enrichment of regulatory marks is correlated with enrichment of conserved blocks in the first intron; the enrichments of conservation and regulatory marks in first intron are not entirely explained by a general, albeit variable, bias for certain marks toward the 5’ end of introns. Interestingly, conservation as well as proportions of active regulatory chromatin marks in the first intron of a gene correlates positively with the numbers of exons in the gene but the correlation is significantly weakened in second introns and negligible beyond the second intron. The first intron conservation is also positively correlated with the gene’s expression level in several human tissues. Finally, a gene-wise analysis shows significant enrichments of active chromatin marks in conserved regions of first introns, relative to the conserved regions in other introns of the same gene. Taken together, our analyses strongly suggest that first introns are enriched for active transcriptional regulatory signals under purifying selection. The online version of this article (doi:10.1186/1471-2164-15-526) contains supplementary material, which is available to authorized users.
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