Massive transcriptional start site analysis of human genes in hypoxia cells

Katsuya Tsuchihara, Yutaka Suzuki, Hiroyuki Wakaguri, Takuma Irie, Kousuke Tanimoto, Shin Ichi Hashimoto, Kouji Matsushima, Junko Mizushima-Sugano, Riu Yamashita, Kenta Nakai, David Bentley, Hiroyasu Esumi, Sumio Sugano

研究成果: Article査読

81 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2249-2263
ページ数15
ジャーナルNucleic acids research
37
7
DOI
出版ステータスPublished - 2009
外部発表はい

ASJC Scopus subject areas

  • 遺伝学

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