Massive transcriptional start site analysis of human genes in hypoxia cells.
Massive transcriptional start site analysis of human genes in hypoxia cells.
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DOI：
10.1093/nar/gkp066
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发表时间：
2009-04
影响因子：
14.9
通讯作者：
Sugano S
中科院分区：
文献类型：
--
作者：
Tsuchihara K;Suzuki Y;Wakaguri H;Irie T;Tanimoto K;Hashimoto S;Matsushima K;Mizushima-Sugano J;Yamashita R;Nakai K;Bentley D;Esumi H;Sugano S
结合我们的全长cDNA方法和大规模并行测序技术，我们开发了一种简单的方法，以高通量的方式收集精确的位置信息的转录起始位点（TSS）的基因表达水平的数字信息。我们应用这种方法观察在常氧和缺氧条件下培养的结肠癌细胞系中基因表达的变化。我们产生了超过1亿个36碱基的TSS标签序列，并揭示了人类基因组转录景观中缺氧反应性改变的综合特征。这些特征包括在54个基因组区域中存在可诱导的“热区域”，220个可能驱动非蛋白编码转录物的新型缺氧诱导型启动子，191个缺氧响应替代启动子以及120个新型和已知缺氧响应基因的详细视图。我们进一步使用额外的6000万个TSS标签分析了不同细胞的缺氧反应，发现基因表达变化的程度在细胞系之间是不同的，这可能反映了细胞对缺氧的鲁棒性。人类基因转录组的新动态图将加深我们对人类基因组转录程序的理解，并为缺氧条件下的癌细胞生物学带来新的见解。
Combining our full-length cDNA method and the massively parallel sequencing technology, we developed a simple method to collect precise positional information of transcriptional start sites (TSSs) together with digital information of the gene-expression levels in a high throughput manner. We applied this method to observe gene-expression changes in a colon cancer cell line cultured in normoxic and hypoxic conditions. We generated more than 100 million 36-base TSS-tag sequences and revealed comprehensive features of hypoxia responsive alterations in the transcriptional landscape of the human genome. The features include presence of inducible ‘hot regions’ in 54 genomic regions, 220 novel hypoxia inducible promoters that may drive non-protein-coding transcripts, 191 hypoxia responsive alternative promoters and detailed views of 120 novel as well as known hypoxia responsive genes. We further analyzed hypoxic response of different cells using additional 60 million TSS-tags and found that the degree of the gene-expression changes were different among cell lines, possibly reflecting cellular robustness against hypoxia. The novel dynamic figure of the human gene transcriptome will deepen our understanding of the transcriptional program of the human genome as well as bringing new insights into the biology of cancer cells in hypoxia.
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通讯作者：
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通讯作者：
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Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
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通讯作者：
Enright, Anton J.