Genome-wide characterization of transcriptional start sites in humans by integrative transcriptome analysis
Genome-wide characterization of transcriptional start sites in humans by integrative transcriptome analysis
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DOI：
10.1101/gr.110254.110
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发表时间：
2011-05-01
期刊：
影响因子：
7
通讯作者：
Suzuki, Yutaka
中科院分区：
文献类型：
--
作者：
Yamashita, Riu;Sathira, Nuankanya P.;Suzuki, Yutaka
我们通过多方面使用大规模并行测序仪对人类基因中的转录起始点(TSS)进行了全基因组分析。通过分析从不同类型的转录组分析中获得的8亿个序列，我们描述了12种人类细胞类型的1.4亿个TSS标签。尽管有大量的TSS簇(TSC)，但TSCs的数量随着表达水平的增加而急剧减少。高表达的TSC表现出几个特征：核小体-SEQ分析揭示了高度有序的核小体结构，CHIP-SEQ分析在其周围区域检测到明显的RNA聚合酶II结合信号，对先前测序和新测序的完整cDNA序列的评估表明它们编码更适合蛋白质翻译的转录本，而对多聚体掺入的RNA的RNA-SEQ分析直接证明这些转录本实际上被翻译成蛋白质。我们还证明了对转录组数据的综合解释对于推定的替代启动子TSCs的选择是必不可少的，其中两个也具有蛋白质后果。此外，在基因TSCs和基因间TSCs中发现了区分不同表达水平的TSCs的染色质特征。所收集的综合信息应该为未来TSCs的生物学特性提供有用的基础。
We performed a genome-wide analysis of transcriptional start sites (TSSs) in human genes by multifaceted use of a massively parallel sequencer. By analyzing 800 million sequences that were obtained from various types of transcriptome analyses, we characterized 140 million TSS tags in 12 human cell types. Despite the large number of TSS clusters (TSCs), the number of TSCs was observed to decrease sharply with increasing expression levels. Highly expressed TSCs exhibited several characteristic features: Nucleosome-seq analysis revealed highly ordered nucleosome structures, ChIP-seq analysis detected clear RNA polymerase II binding signals in their surrounding regions, evaluations of previously sequenced and newly shotgun-sequenced complete cDNA sequences showed that they encode preferable transcripts for protein translation, and RNA-seq analysis of polysome-incorporated RNAs yielded direct evidence that those transcripts are actually translated into proteins. We also demonstrate that integrative interpretation of transcriptome data is essential for the selection of putative alternative promoter TSCs, two of which also have protein consequences. Furthermore, discriminative chromatin features that separate TSCs at different expression levels were found for both genic TSCs and intergenic TSCs. The collected integrative information should provide a useful basis for future biological characterization of TSCs.