Structure basis of maintenance DNA methylation

• Project/Area Number: 21247013
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Kyoto University
• Principal Investigator: SHIRAKAWA Masahiro 京都大学, 大学院・工学研究科, 教授 (00202119)
• Co-Investigator(Renkei-kenkyūsha): ARIYOSHI Mariko 京都大学, 物質-細胞統合システム拠点, 特任准教授 (80437243)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000); Fiscal Year 2011: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2010: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: DNAメチル化 / エピジェネティック / ヒストン / X線結晶解析 / NMR / エピジェネティクス / ヒストン修飾 / 構造生物学

Research Abstract

DNA methylation and histone modifications are epigenetic marks that maintain an epigenetic state in each differentiated cell. We investigated structures and functions of two key proteins in maintenance and regulation of DNA methylation patterns ; a hemi-methylated DNA binding protein, UHRF1 and one of methyl CpG binding domain proteins, MBD4. Our structural and biochemical data have shed light on a combinatorial recognition of two histone modifications by UHRF1. Furthermore our research have gained structural basis of versatile base recognition of MBD4.

Research Products

• [Journal Article] NMR analysis of Lys63-linked polyubiquitin recognition by the tandem ubiquitin-interacting motifs of Rap80. (2012)
  • Author(s): Sekiyama N, Jee J, Isogai S, Akagi K, Huang TH, Ariyoshi M, Tochio H, Shirakawa M.
  • Journal Title: J Biomol NMR. Volume: 52 Issue: 4 Pages: 339-350
  • DOI: 10.1007/s10858-012-9614-9
  • Peer Reviewed
• [Journal Article] Crystal structure of the UBA domain of p62 and its interaction with ubiquitin (2011)
  • Author(s): Isogai, S., Morimoto, D., Arita, K., Unzai, S., Tenno, T., Hasegawa, J., Sou, Y.S., Komatsu, M., Tanaka, K., Shirakawa, M., Tochio, H.
  • Journal Title: J Biol Chem. Volume: 286 Issue: 36 Pages: 31864-318674
  • DOI: 10.1074/jbc.m111.259630
  • Peer Reviewed
• [Journal Article] Structural basis for regulation of poly-SUMO chain by a SUMO-like domain of Nip45 (2010)
  • Author(s): Sekiyama, N., Arita, K., Ikeda, Y., Hashiguchi, K., Ariyoshi, M., Tochio, H., Saitoh, H. and Shirakawa, M.
  • Journal Title: Proteins : Structure, Function, and Bioinformatics 78 Volume: 78 Issue: 6 Pages: 1491-1502
  • DOI: 10.1002/prot.22667
  • Peer Reviewed
• [Journal Article] Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable to identify the key residues for binding to replicative helicase Mcm proteins (2010)
  • Author(s): Jee, J.-G., Mizuno, T., Kamada, K., Tochio, T., Chiba, Y., Yanagi, K., Yasuda, G., Hiroaki, H., Hanaoka, F. and Shirakawa, M
  • Journal Title: Journal of Biological Chemistry Volume: vol.285(21) Issue: 21 Pages: 15931-40
  • DOI: 10.1074/jbc.m109.075333
  • Peer Reviewed
• [Journal Article] Purification, crystallization and preliminary crystallographic studies of Lys48-linked polyubiquitin chains (2010)
  • Author(s): Morimoto, D., Isogai, S., Tenno, T., Tochio, H., Shirakawa, M., Ariyoshi, M.
  • Journal Title: Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun Volume: vol.66(Pt7) Issue: 7 Pages: 834-7
  • DOI: 10.1107/s1744309110018804
  • Peer Reviewed
• [Journal Article] エピジェネティック制御における分子認識:DNAメチル化制御の構造生物学 (2010)
  • Author(s): 有吉眞理子、白川昌宏
  • Journal Title: 実験医学増刊 Volume: Vol.28(15) Pages: 107-114
• [Journal Article] Solution structure of a zinc-finger domain that binds to poly-ADP-ribose (2010)
  • Author(s): Isogai S, Kanno S, Ariyoshi M, Tochio H, Ito Y, Yasui A, Shirakawa M.
  • Journal Title: Genes Cells. Volume: 15(2) Issue: 2 Pages: 101-10
  • DOI: 10.1111/j.1365-2443.2009.01369.x
  • Peer Reviewed
• [Journal Article] Structural basis for regulation of poly-SUMO chain by a SUMO-like domain of Nip45. (2010)
  • Author(s): Sekiyama N, Arita K, Ikeda Y, Hashiguchi K, Ariyoshi M, Tochio H, Saitoh H, Shirakawa M.
  • Journal Title: Proteins Volume: 78 Pages: 1491-1502
  • Peer Reviewed
• [Journal Article] Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable the identification of key residues for binding to replicative helicase Mcm proteins. (2010)
  • Author(s): Jee J, Mizuno T, Kamada K, Tochio H, Chiba Y, Yanagi K, Yasuda G, Hiroaki H, Hanaoka F, Shirakawa M
  • Journal Title: J Biol Chem Volume: 285 Pages: 15931-15940
  • Peer Reviewed
• [Journal Article] Purification, crystallization and preliminary crystallographic studies of Lys48-linked polyubiquitin chains. (2010)
  • Author(s): Morimoto D, Isogai S, Tenno T, Tochio H, Shirakawa M, Ariyoshi M.
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun. Volume: 66 Pages: 834-837
  • Peer Reviewed
• [Journal Article] エピジェネティック制御における分子認識:DNAメチル化制御の構造生物学 (2010)
  • Author(s): 有吉眞理子、白川昌宏
  • Journal Title: 実験医学 Volume: 18 Pages: 107-114
• [Journal Article] Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable to identify the key residues for binding to replicative helicase Mcm proteins (2010)
  • Author(s): Jee, J.-G., Mizuno, T., Kamada, K., Tochio, T., Chiba, Y., Yanagi, K., Yasuda, G., Hiroaki, H., Hanaoka, F., Shirakawa, M.
  • Journal Title: Journal of Biological Chemistry (pub ahead of print in 2010)
  • Peer Reviewed
• [Journal Article] Structural basis for regulation of poly-SUMO chain by a SUMO-like domain of Nip45. (2010)
  • Author(s): Sekiyama, N., Aria, K, Ikeda, Y., Hashiguchi, K., Ariyoshi, M., Tochio, H., Saitoh, H., Shirakawa, M.
  • Journal Title: Proteins : Structure, Function, and Bioinformatics 78 Pages: 1491-1502
  • Peer Reviewed
• [Journal Article] Solution structure of a zinc+finger domain that binds to poly-ADP-ribose. (2010)
  • Author(s): Isogai, S., Kanno, S., Ariyoshi, M., Tochio, H., Ito, Y., Yasui, A., Shirakawa, M.
  • Journal Title: Genes to Cells 15 Pages: 101-110
  • Peer Reviewed
• [Presentation] (2010)
  • Author(s): 有田恭平, 杉田和也, 鵜木元香, 浜本隆二, 有吉眞理子, 杤尾豪人, 白川昌宏
  • Organizer: 第33回分子生物学会年会,第83回日本生化学会年会、合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-10
• [Presentation] UHRF1によるエピジェネティックマークの読み取り機構の構造生物学 (2010)
  • Author(s): 有田恭平, 杉田和也, 鵜木元香, 浜本隆二, 有吉眞理子, 朽尾豪人, 白川昌宏
  • Organizer: 第33回分子生物学会年会,第83回日本生化学会年会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-10
• [Presentation] Structural biology of epigenetic regulations and NMR observation of proteins in eukaryotic cells (2010)
  • Author(s): Masahiro Shirakawa
  • Organizer: APRU research symposium
  • Place of Presentation: Kyoto University, Japan
  • Year and Date: 2010-11-24
• [Presentation] Plenary lecture (2010)
  • Author(s): Masahiro Shirakawa
  • Organizer: APRU research symposium
  • Place of Presentation: Kyoto University, Japan
  • Year and Date: 2010-11-24