The structural study of heterochromatin by cryo-EM

• Project/Area Number: 16K18473
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Genome biology
• Research Institution: Waseda University
• Principal Investigator: Machida Shinichi 早稲田大学, 理工学術院, 助教 (50732195)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: エピジェネティクス / クロマチン / ヒストン / ヘテロクロマチン / HP1 / ヒストン修飾 / ヌクレオソーム / H3K9me3

Outline of Final Research Achievements

Heterochromatin functions as an important component for gene silencing and genome maintenance by the formation of condensed chromatin structures. The methylation of histone H3 at lysine 9 (H3K9me3) and its recognition by HP1 represent heterochromatin formation. However, it is unclear how HP1 folds chromatin containing H3K9me3 into condensed chromatin. In this study, we reconstituted H3K9me3 chromatin complexed with human HP1, and determined the structure of H3K9me3 chromatin complexed with HP1 by cryogenic electron microscopy.

Research Products

• [Journal Article] Cryo-EM structure of the nucleosome containing the ALB1 enhancer DNA sequence (2018)
  • Author(s): Takizawa Yoshimasa、Tanaka Hiroki、Machida Shinichi、Koyama Masako、Maehara Kazumitsu、Ohkawa Yasuyuki、Wade Paul A.、Wolf Matthias、Kurumizaka Hitoshi
  • Journal Title: Open Biology Volume: 8 Issue: 3 Pages: 170255-170255
  • DOI: 10.1098/rsob.170255
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural Basis of Heterochromatin Formation by Human HP1 (2018)
  • Author(s): Machida Shinichi、Takizawa Yoshimasa、Ishimaru Masakazu、Sugita Yukihiko、Sekine Satoshi、Nakayama Jun-ichi、Wolf Matthias、Kurumizaka Hitoshi
  • Journal Title: Molecular Cell Volume: 69 Issue: 3 Pages: 385-397
  • DOI: 10.1016/j.molcel.2017.12.011
  • Peer Reviewed
• [Journal Article] HP1との結合により形成される構成的なヘテロクロマチンの基盤となる構造 (2018)
  • Author(s): 町田晋一, 滝沢由政, Matthias Wolf, 胡桃坂仁志
  • Journal Title: First Author's Volume: . Pages: 014
  • DOI: 10.7875/first.author.2018.014
  • Peer Reviewed / Open Access
• [Journal Article] Phosphorylation of CBX2 controls its nucleosome-binding specificity (2017)
  • Author(s): Takayuki Kawaguchi, Shinichi Machida, Hitoshi Kurumizaka, Hideaki Tagami, Jun-ichi Nakayama
  • Journal Title: The Journal of Biochemistry Volume: 162 Issue: 5 Pages: 343-355
  • DOI: 10.1093/jb/mvx040
  • NAID: 40021394855
  • Peer Reviewed
• [Journal Article] Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes. (2017)
  • Author(s): Hatanaka Y, Tsusaka T, Shimizu N, Morita K, Suzuki T, Machida S, Satoh M, Honda A, Hirose M, Kamimura S, Ogonuki N, Nakamura T, Inoue K, Hosoi Y, Dohmae N, Nakano T, Kurumizaka H, Matsumoto K, Shinkai Y, Ogura A.
  • Journal Title: Cell Rep Volume: 20(12) Issue: 12 Pages: 2756-2765
  • DOI: 10.1016/j.celrep.2017.08.088
  • Peer Reviewed / Open Access
• [Journal Article] SYCP3 regulates strand invasion activities of RAD51 and DMC1 (2017)
  • Author(s): Kobayashi Wataru、Hosoya Noriko、Machida Shinichi、Miyagawa Kiyoshi、Kurumizaka Hitoshi
  • Journal Title: Genes to Cells Volume: 22 Issue: 9 Pages: 799-809
  • DOI: 10.1111/gtc.12513
  • Peer Reviewed / Open Access
• [Journal Article] Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3. (2017)
  • Author(s): Kakumu E
  • Journal Title: Genes Cells. Volume: 3 Issue: 3 Pages: 310-327
  • DOI: 10.1111/gtc.12479
  • Peer Reviewed / Open Access
• [Journal Article] Influence of polynucleosome preparation methods on sedimentation velocity analysis of chromatin. (2017)
  • Author(s): Kujirai T, Machida S, Osakabe A, Kurumizaka H.
  • Journal Title: J. Biochem. Volume: 161 Issue: 4 Pages: 381-388
  • DOI: 10.1093/jb/mvw081
  • NAID: 40021219908
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis (2017)
  • Author(s): Ueda J., Harada A., Urahama T., Machida S., Maehara K., Hada M., Makino Y., Nogami J., Horikoshi N., Osakabe A., Taguchi H., Tanaka H., Tachiwana H., Yao T., Yamada M., Iwamoto T., Isotani A., Ikawa M., Tachibana T., Okada Y., Kimura H., Ohkawa Y., Kurumizaka H., Yamagata K.
  • Journal Title: Cell Reports Volume: 18(3) Issue: 3 Pages: 593-600
  • DOI: 10.1016/j.celrep.2016.12.065
  • NAID: 120006957416
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chromatin architecture may dictate the target site for DMC1, but not for RAD51, during homologous pairing (2016)
  • Author(s): Kobayashi W., Takaku M., Machida S., Tachiwana H., Maehara K., Ohkawa Y. and Kurumizaka H
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 24428-24428
  • DOI: 10.1038/srep24228
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural and biochemical analyses of monoubiquitinated human histones H2B and H4 (2016)
  • Author(s): Machida S, Sekine S, Nishiyama Y, Horikoshi N, Kurumizaka H.
  • Journal Title: Open Biol. Volume: 6 Issue: 6 Pages: 160090-160090
  • DOI: 10.1098/rsob.160090
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ヘテロクロマチンの立体構造解析 (2017)
  • Author(s): 町田晋一、滝沢由政、石丸雅一、関根慧、中山潤一、Matthias Wolf、胡桃坂仁志
  • Organizer: 第11回日本エピジェネティクス研究会年会
• [Remarks] 早稲田大学ホームページ
  • URL: https://www.waseda.jp/top/news/56537
• [Remarks] 沖縄科学技術大学院大学ホームページ
  • URL: https://www.oist.jp/ja/news-center/press-releases/32226
• [Remarks] 基礎生物学研究所ホームページ
  • URL: http://www.nibb.ac.jp/press/2018/01/11.html