Development of a new therapy by regulating histone acetylation

• Project/Area Number: 26293166
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Osaka University
• Principal Investigator: ISAKA Yoshitaka 大阪大学, 医学(系)研究科(研究院), 教授 (00379166)
• Co-Investigator(Kenkyū-buntansha): 貝森 淳哉 大阪大学, 医学(系)研究科(研究院), 寄附講座准教授 (70527697)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Hiroshi 東京工業大学, 科学技術創成研究院, 教授 (30241392)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 腎障害 / エピジェネティク / ヒストン修飾 / 細胞肥大 / エピジェネティック / ｴﾋﾟｼﾞｪﾈﾃｨｸｽ / 腎臓内科 / エピジェネティクス

Outline of Final Research Achievements

Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20 (H4K20ac), a major methylation site, can also be acetylated. To understand the function of H4K20ac, we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes. The distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations. A motif search in H4K20ac-enriched sequences, together with transcription factor binding profiles based on ENCODE ChIP-seq data, revealed that most transcription activators are excluded from H4K20ac-enriched genes and a transcription repressor NRSF/REST co-localized with H4K20ac.

Research Products

• [Journal Article] Histone H4 lysine 20 acetylation is associated with gene repression in human cells. (2016)
  • Author(s): Kaimori, J. Y., Maehara, K., Hayashi-Takanaka, Y., Harada, A., Fukuda, M., Yamamoto, S., Ichimaru, N., Umehara, T., Yokoyama, S., Matsuda, R., Ikura, T., Nagao, K., Obuse, C., Nozaki, N., Takahara, S., Takao, T., Ohkawa, Y., Kimura, H., and Isaka, Y.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 24318-24318
  • DOI: 10.1038/srep24318
  • NAID: 120005770760
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Histone H4 lysine 20 acetylation is associated with gene repression in human cells. (2016)
  • Author(s): Kaimori J, Maehara K, Hayashi-Takanaka Y, Harada A, Fukuda M, Yamamoto S, Ichimaru N, Umehara T, Yokoyama S, Matsuda R, Ikura T, Nagao K, Obuse C, Nozak Ni, akahara S, Takao T, Ohkawa Y, Kimura H, and Isaka Y
  • Journal Title: Scientific Reports Volume: in press
  • NAID: 120005770760
  • Peer Reviewed / Open Access / Acknowledgement Compliant