Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes
Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes
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DOI：
10.1101/gr.4039406
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发表时间：
2006-01-01
期刊：
影响因子：
7
通讯作者：
Sugano, S
中科院分区：
文献类型：
--
作者：
Kimura, K;Wakamatsu, A;Sugano, S
通过分析164种oligo-cap cDNA文库中的1，780，295个人全长cDNA的S '端序列，我们确定了14，628个人RefSeq基因的269，774个独立的转录起始位点（TSS）。这些TSS被聚类成30，964个簇，这些簇彼此分开超过500 bp，因此很可能构成相互不同的替代启动子。令人惊讶的是，至少7674（52%）个人RefSeq基因受到推定替代启动子（PAPs）的调控。平均而言，每个基因有3.1个PAP，每2.6个无CpG启动子有一个含CpG岛的启动子。在17%的含有PAP的位点中，观察到PAP的组织特异性使用。组织特异性PAP最丰富的组织来源是睾丸和脑。同样有趣的是，含有PAP的启动子在编码信号转导相关蛋白的基因中富集，而在编码胞外蛋白的基因中较少，这可能分别反映了这些类别基因的不同功能要求和有限表达。第一外显子的模式也是高度多样的。平均每个基因座有7.7种不同的第一外显子剪接类型，这表明PAPs可能通过这种机制产生多种转录物。我们的研究结果表明，使用替代启动子和随后的第一外显子的替代使用应该在产生人类高度复杂的分子系统所需的复杂性方面发挥关键作用。
By analyzing 1,780,295 S'-end Sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 Clusters that were separated from each other by more than 500 bp and thus are very likely to Constitute Mutually distinct alternative promoters. To Our Surprise, at least 7674 (52%) human RefSeq genes were Subject to regulation by Putative alternative promoters (PAPs). Oil average, there were 3.1 PAPs per gene, with the composition of one CpG-island-containing promoter per 2.6 CpG-less promoters. In 17% of the PAP-containing loci, tissue&specific use of the PAPs was observed. The richest tissue Sources of the tissue-specific PAPs were testis and brain. It was also intriguing that the PAP-containing promoters were enriched in the genes encoding signal transduction-related proteins and were rarer in the genes encoding extracellular proteins, possibly reflecting the varied functional requirement for and the restricted expression of those categories of genes, respectively. The patterns of the first exons were highly diverse as well. Oil average, there were 7.7 different splicing types of first exons per locus partly produced by the PAPs, Suggesting that a wide variety of transcripts call be achieved by this mechanism. Our findings Suggest that use of alternate promoters and consequent alternative use of first exons Should play a pivotal role in generating the complexity required for the highly elaborated molecular systems in humans.