Role of histone modifications on establishing DNA methylation patterns

2011 Fiscal Year Final Research Report

• Project/Area Number: 21570136
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: SUETAKE Isao 大阪大学, 蛋白質研究所, 准教授 (80304054)
• Project Period (FY): 2009 – 2011
• Keywords: DNAメチル化

Research Abstract

Dnmt3a creates DNA methylation patterns. Dnmt3a2, an isoform of Dnmt3a, lacks amino-terminal 219 amino acids of Dnmt3a and is highly expressed in germ cells and early embryo. We found that the amino-terminal 219 amino acids shows DNA binding activity and contributes for its localization and for DNA methylation activity. On the other hands, DNA methylation pattern once created is maintained by Dnmt1. We solved crystal structure of mouse Dnmt1(291-1602 amino acids) at 1. 3 A resolution. Notably, in the absence of DNA, the amino-terminal domain responsible for targeting Dnmt1 to replication foci is inserted into the DNA-binding pocket, indicating that this domain must be removed during methylation reaction.

Research Products

• [Journal Article] The Dnmt3b Splice Variant is Specifically Expressed in In Vitro-manipulated Blastocysts and Their Derivative ES Cells (2011)
  • Author(s): Horii T, Suetake I, Yanagisawa E, Morita S, Kimura M, Nagao Y, Imai H, Tajima S, and Hatada I
  • Journal Title: J. Reprod. Dev Volume: 57 Pages: 579-585
  • DOI: DOI:10.1262/jrd.10-194A
  • Peer Reviewed
• [Journal Article] Characterization of DNA-binding activity in the N-terminal domain of DNA methyltransferase Dnmt3a (2011)
  • Author(s): Suetake I, Mishima Y, Kimura H, Lee Y, Goto Y, Takeshima H, Ikegami T, and Tajima S
  • Journal Title: Biochem. J Volume: 437 Pages: 141-148
  • DOI: DOI:0.1042/BJ20110241
• [Journal Article] Structual insight into maintenance methylation by mouse DNA methyltransferase(Dnmt1) (2011)
  • Author(s): Takeshita K, Suetake I, Yamashita E, Suga M, Narita H, Nakagawa A, and Tajima S
  • Journal Title: PNAS Volume: 108 Pages: 9055-9059
  • DOI: DOI:10.1073/pnas.1019629108
  • Peer Reviewed
• [Journal Article] Recombinant mammalian DNA methyltransferase activity on model transcriptional gene silencing short RNA : DNA hybrid substrates (2010)
  • Author(s): Ross J, Suetake I, Tajima S, and Molloy PL
  • Journal Title: Biochem. J Volume: 432 Pages: 323-332
  • DOI: DOI:10.1042/BJ20100579
  • Peer Reviewed
• [Journal Article] Array-based genomic resequencing of human leukemia (2010)
  • Author(s): Yamashita Y, Yuan J, Suetake I, Suzuki H, Ishikawa Y, Choi Y L, Ueno T, Soda M, Hamada T, Haruta H, Takada S, Miyazaki Y, Kiyoi H, Ito E, Naoe T, Tomonaga M, Toyota M, Tajima S, Iwama A, and Mano H
  • Journal Title: Oncogene Volume: 29 Pages: 3723-3731
  • DOI: DOI:10.1038/onc.2010.117
  • Peer Reviewed
• [Journal Article] The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/ epsilon (2010)
  • Author(s): Sugiyama Y, Hatano N, Sueyoshi N, Suetake I, Tajima S, Kinoshita E, Kinoshita-Kikuta E, Koike T, and Kameshita I
  • Journal Title: Biochem J Volume: 427 Pages: 489-497
  • DOI: DOI:10.1042/BJ20091856
  • Peer Reviewed
• [Presentation] Dnmt1によるDNA維持メチル化のin vivoにおける責任領域 (2012)
  • Author(s): 長谷川貴志、木村博信、末武勲、武藤正弘、ジャファルシャリフ、古関明彦、田嶋正二
  • Organizer: 第6回日本エピジェネティクス研究会年会
  • Place of Presentation: 学術総合センター
  • Year and Date: 20120514-15
• [Presentation] ポリコーム群蛋白質複合体(PRC2)によるヒストンH3K27メチル化活性-Suz12の責任領域- (2012)
  • Author(s): 三島優一、磯野協一、古関明彦、田嶋正二、末武勲
  • Organizer: 第6回日本エピジェネティクス研究会年会
  • Place of Presentation: 学術総合センター
  • Year and Date: 20120514-15
• [Presentation] Dnmt1によるDNA維持メチル化活性は領域の大きな再配置を伴う反応である (2012)
  • Author(s): 末武勲、中村達郎、ベルキュレクアハメトジャン、竹下浩平、中川敦史、田嶋正二
  • Organizer: 第6回日本エピジェネティクス研究会年会
  • Place of Presentation: 学術総合センター
  • Year and Date: 20120514-15
• [Presentation] 海洋無脊椎動物からのDnmt1阻害剤の探索 (2012)
  • Author(s): 石上進太郎、末武勲、田嶋正二、中尾洋一
  • Organizer: 第6回日本エピジェネティクス研究会年会
  • Place of Presentation: 学術総合センター
  • Year and Date: 20120514-15
• [Presentation] X線結晶構造から見るDnmt1のエピジェネティックマーク継承のメカニズム (2011)
  • Author(s): 竹下浩平、末武勲、山下栄樹、菅倫寛、成田宏隆、中川敦史、田嶋正二
  • Organizer: 第49回生物物理学会年会
  • Place of Presentation: 兵庫県立大学書写キャンパス
  • Year and Date: 20110916-18
• [Presentation] Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (2011)
  • Author(s): Takeshita, K., Suetake, I., Yamashita, E., Suga, M., Narita, H., Nakagawa, A., Tajima, S.
  • Organizer: International Union of Crystallography(IUCr)
  • Place of Presentation: Madrid Spain
  • Year and Date: 20110822-30
• [Presentation] Dnmt1によるメチル化模様維持機構に関する構造生物学的研究 (2011)
  • Author(s): 竹下浩平、末武勲、山下栄樹、菅倫寛、成田宏隆、中川敦史、田嶋正二
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: ホテル阪急エキスポパーク
  • Year and Date: 20110607-09
• [Presentation] X線結晶構造から考察するDnmt1による維持メチル化機構 (2011)
  • Author(s): 竹下浩平、末武勲、山下栄樹、菅倫寛、成田宏隆、中川敦史、田嶋正二
  • Organizer: 第5回日本エピジェネティクス研究会年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] 再構成ヌクレオソームに対するヘテロクロマチン蛋白質1の結合様式 (2011)
  • Author(s): 三島優一、Chanika D Jayasinge、川上徹、大谷淳二、菊川雄介、白川昌宏、木村宏、相本三郎、田嶋正二、末武勲
  • Organizer: 第5回エピジェネティクス年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] Inhibitory effect of chromo shadow domain of heteromchromatin protein 1γ(HP1γ) on its recognition of the trimethlyated lysine 9 of histone H3 in nucleosome structure (2011)
  • Author(s): Chanika Jayasinghe, Yuichi Mishima, Junji Otani, Yusuke Kikugawa, Masahiro Shirakawa, Shoji Tajima, and Isao Suetake
  • Organizer: 第5回エピジェネティクス年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] X線結晶構造から考察するDnmt1による維持メチル化機構 (2011)
  • Author(s): 竹下浩平、末武勲、山下永樹、菅倫寛、成田宏隆、中川敦史、田嶋正二
  • Organizer: 第5回エピジェネティクス年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] Denovo型DNAメチル化酵素Dnmt3a2とコリプレッサー蛋白質Trim28の結合様式の検討 (2011)
  • Author(s): 木村博信、末武勲、田嶋正二
  • Organizer: 第5回エピジェネティクス年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] Dnmt1とNp95/ Uhrf1の機能的相互作用、ベルキュレクアハマトジャン (2011)
  • Author(s): 竹谷和博、西尾チカ、末武勲、田嶋正二
  • Organizer: 第5回エピジェネティクス年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] Dnmt1の活性にはたす複製フォーク標的化シグナル(RFTS)の役割 (2011)
  • Author(s): 中村達郎、末武勲、田嶋正二
  • Organizer: 第5回エピジェネティクス年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] メチル化CpG結合蛋白質MBD4によるDNA認識の構造的基盤 (2011)
  • Author(s): 大谷淳二、有田恭平、有吉眞理子、木村博信、末武勲、田嶋正二、白川昌宏
  • Organizer: 第5回エピジェネティクス年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Presentation] Binding specificities of heterochromatin protein 1a, b, and g to the reconstituted nucleosomes containing tri-methylated lysine 9 histone H3 (2010)
  • Author(s): Yuichi Mishima, Makoto Watanabe, Toru Kawakami, Yuko Aoki, Hiroshi Kimura, Saburo Aimoto, Osamu Nishimura, Shoji Tajima, Isao Sueta
  • Organizer: JSPS Sweden-Japan joint colloquium" epigenetics. new horizon in Japan and Scandinavia"
  • Place of Presentation: nobel forum, karolonska institute, Stockholm
  • Year and Date: 20100906-07
• [Presentation] トリメチル化リシン9をもつ再構成ヌクレオソームに対するheterochromatin protein 1の特異的な結合様式 (2010)
  • Author(s): 三島優一、渡辺真、川上徹、青木優子、木村宏、相本三郎、西村紀、田嶋正二、末武勲
  • Organizer: 第4回エピジェネティクス研究会
  • Place of Presentation: 米子市文化ホール
  • Year and Date: 20100528-29
• [Presentation] Histone H3K9 trimethylation stimulates the histone H3K27 methylation activity of PRC2 bypassing Eed (2010)
  • Author(s): I Suetake ; S Aimoto ; Y Aoki ; K Isano ; T Kawakami ; H Kimura ; H Koseki ; Y Mishima ; O Nishimura ; S Tajima ; M Watanabe
  • Organizer: Keystone symposium
  • Place of Presentation: Sagebrush Inn and Conference Center, Taos, New Mexico
  • Year and Date: 20100117-22
• [Presentation] ポリコーム群蛋白質複合体PRC2によるヒストンH3メチル化活性に対する、ヒストンH3の9番目のリシン残基のトリメチル化修飾の影響 (2009)
  • Author(s): 三島優一、田嶋正二、末武勲
  • Organizer: 第3回日本エピジェネティクス研究会年会
  • Place of Presentation: 学術総合センター
  • Year and Date: 20090522-23