5'-end transcriptome and DNA methylation in cells treated with histone deacetylase inhibitor.

• Project/Area Number: 21510202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 基礎ゲノム科学
• Research Institution: Kanazawa University (2011); The University of Tokyo (2009-2010)
• Principal Investigator: HASHIMOTO Shinichi 金沢大学, 医学系, 特任教授 (00313099)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝子発現 / DNAメチル化 / 脱アセチル化阻害剤 / 次世代DNAシーケンサー / エピジェネティクス / トランスクリプトーム / 次世DNAシーケンサー / 次世代超高速DNAシーケンサー

Research Abstract

Here, we performed the high-resolution study of 5'-end transcriptome and DNA methylation state of genome in a human colon cancer cell line, HT-29 treated with a HDACi, trichostatin A(TSA) by using next-generation sequencer. More than 20 million 25 base 5'-end tags were obtained from two libraries and matched to the human genome. The expression of 2, 426 genes, which corresponded to 16% of all expressed genes in a single cell type, differed significantly between the control and TSA-treated cells. Next, when we analyzed the functional relationship between their differential expression and the DNA methylation of associated genes by using newly developed MSDS, change of gene expression by TSA did not correlate with genome-wide of DNA methylation status, suggesting that demethylation limited sites may be specifically regulated by TSA leading to be change of particular genes.

Research Products

• [Journal Article] Genome wide profiling of DNA methylation in human cancer cells (2011)
  • Author(s): Ogoshi, K., Hashimoto, S., Nakai, K., Qu, W., Oshima, K., Tokunaga, K., Sugano, S., Hattrori, M., Morishita, S., and Matsushima, K.
  • Journal Title: Genomics Volume: 98 Pages: 280-287
  • Peer Reviewed
• [Journal Article] Genome-wide characterization of transcriptional start sites in humans by integrative transcriptome analysis (2011)
  • Author(s): Yamashita, R., Sathira, N. P., Kanai, A., Tanimoto, K., Arauchi, T., Tanaka, Y., Hashimoto, S., Sugano, S., Nakai, K., and Suzuki, Y.
  • Journal Title: Genome Res Volume: 21 Pages: 775-789
  • Peer Reviewed
• [Journal Article] Genome-wide characterization of transcriptional start sites in human by integrative transcriptome analysis (2011)
  • Author(s): Yamashita, R., et al.
  • Journal Title: Genome Research
  • Peer Reviewed
• [Journal Article] Comprehensive gene expression analysis of 5'-end of mRNA identified novel intronic transcripts associated with hepatocellular carcinoma (2010)
  • Author(s): Hodo, Y., Hashimoto, S., Honda, M., Yamashita, T., Suzuki, Y., Sugano, S., Kaneko, S., and Matsushima, K.
  • Journal Title: Genomics Volume: 95 Pages: 217-223
  • NAID: 120002086414
  • Peer Reviewed
• [Journal Article] Genome-wide high-resolution transcriptional start sites mapping of cells under hypoxia condition (2009)
  • Author(s): Tsuchihara, K., Suzuki, Y., Wakaguri, H., Irie, T., Hashimoto, S., Matsushima, K., Mizushima-Sugano, J., Yamashita, R., Nakai, K., Bentley, D., Esumi, H., and Sugano, S.
  • Journal Title: Nucleic Acids Res Volume: 37 Pages: 2249-2263
  • Peer Reviewed
• [Journal Article] Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites (2009)
  • Author(s): Sasaki, S., Mello, C. C., Shimada, A., Nakatani, Y., Hashimoto, S., Ogawa, M., Matsushima, K., Gu, S. G., Kasahara, M., Ahsan, B., Sasaki, A., Saito, T., Suzuki, Y., Sugano, S., Kohara, Y., Takeda, H., Fire, A., and Morishita, S.
  • Journal Title: Science Volume: 323 Pages: 401-404
  • Peer Reviewed
• [Journal Article] Efficient frequency-based de novo short-read clustering for error trimming in next-generation sequencing (2009)
  • Author(s): Qu, W., Hashimoto, S., and Morishita, S.
  • Journal Title: Genome Res 19 Pages: 1309-1315
  • Peer Reviewed
• [Journal Article] High-resolution analysis of the 5'-end transcriptome using a next generation DNA sequencer (2009)
  • Author(s): Hashimoto, S., Qu, W., Ahsan, B., Ogoshi, K., Sasaki, A., Nakatani, Y., Lee, Y., Ogawa, M., Ametani, A., Suzuki, Y., Sugano, S., Lee, C. C., Nutter, R. C., Morishita, S., and Matsushima, K.
  • Journal Title: PLoS One 4
  • Peer Reviewed
• [Journal Article] High-resolution analysis of the 5'-end transcriptome using a next generation DNA sequencer. (2009)
  • Author(s): Hashimoto, S., et al.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] Chromatin-Associated Periodicity in Genetic Variation Downstream of Transcriptional Start Sites. (2009)
  • Author(s): Sasaki, S., et al.
  • Journal Title: Science 323 Pages: 401-404
  • Peer Reviewed
• [Journal Article] Genome-wide high-resolution transcriptional start sites mapping of cells under hypoxia condition. (2009)
  • Author(s): Tsuchihara, K., et al.
  • Journal Title: Nucleic Acids Res 37 Pages: 2249-2263
  • Peer Reviewed
• [Presentation] MiR-449 induced by HDACi in colon cancer cell lines mediated cell death (2011)
  • Author(s): 橋本
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2011-10-04
• [Presentation] MiR-449 induced by HDACi in colon cancer cell lines mediated cell death (2011)
  • Author(s): 橋本真一, ら
  • Organizer: 第70回日本癌学会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-04
• [Presentation] Gene expression and DNA methylation profiling in a ca cer cell line treated with TSA using secend generation sequencer (2009)
  • Author(s): 橋本
  • Organizer: 第68回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-12
• [Presentation] Gene expression and DNA methylation profiling in a cancer cell line treated with TSA using second generation sequencer (2009)
  • Author(s): Shin-ichi Hashimoto
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02