Analysis of the regulatory network of cohesin acetylation

• Project/Area Number: 25290065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: Bando Masashige 東京大学, 分子細胞生物学研究所, 助教 (90360627)
• Co-Investigator(Kenkyū-buntansha): NAKATO Ryuichiro 東京大学, 分子細胞生物学研究所, 助教 (60583044)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: コヒーシン / アセチル化 / Esco / 姉妹染色分体間接着 / DNA複製 / MCMヘリカーゼ / ゲノム / Mcmヘリカーゼ / クロマチン / 姉妹染色体 / 転写制御

Outline of Final Research Achievements

There are two cohesin acetyl transferase, Esco1 and Esco2, in human. Both of them are essential for establishment of sister chromatids cohesion. We found that Esco1 directly binds to cohesin subunit Pds5 and co-localizes with cohesin. The domain for binding with Pds5 is responsible for cohesin acetylation and cohesion establishment. Esco1 phosphorylated in mitosis prevents its binding with Pds5. Therefore phosphorylation may have important role in controlling Esco1 localization. Esco2 associates with MCM helicases during G1 to S-phase. The N-terminal domain of Esco2 conserved among vertebrates is required for direct interation with MCM. It has been known that Esco2 is down-regulated from late G2 to M phase. Interestingly Esco2 mutant that is unable to bind to Mcm is destabilized. This destabilization of Esco2 is caused by proteaosome pathway mediated by Cul4 ligase. Thus, Esco1 and Esco2 function in different pathway from each other to promote cell cycle progression.

Research Products

• [Journal Article] Condensin targets and reduces unwound DNA structures associated with transcription in mitotic chromosome condensation (2015)
  • Author(s): Takashi Sutani, Toyonori Sakata, Ryuichiro Nakato, Koji Masuda, Mai Ishibashi, Daisuke Yamashita, Yutaka Suzuki, Tatsuya Hirano, Masashige Bando, Katsuhiko Shirahige
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 1-13
  • DOI: 10.1038/ncomms8815
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco2 (2015)
  • Author(s): Masashi Minamino, Mai Ishibashi, Ryuichiro Nakato, Kazuhiro Akiyama, Hiroshi Tanaka, Yuki Kato, Lumi Negishi, Toru Hirota, Takashi Sutani, Masashige Bando, Katsuhiko Shirahige
  • Journal Title: Current Biology Volume: 25 Issue: 13 Pages: 1694-1706
  • DOI: 10.1016/j.cub.2015.05.017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Deubiquitinating Enzyme USP7 Regulates Androgen Receptor Activity by Modulating Its Binding to Chromatin (2015)
  • Author(s): Shu-Ting Chen, Maiko Okada, Ryuichiro Nakato, Kosuke Izumi, Masashige Bando and Katsuhiko Shirahige
  • Journal Title: Journal of Biological Chemistry Volume: 290 Issue: 35 Pages: 21713-21723
  • DOI: 10.1074/jbc.m114.628255
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. (2015)
  • Author(s): Izumi K, Nakato R, Zhang Z, Edmondson AC, Noon S, Dulik MC, Rajagopalan R, Venditti CP, Gripp K, Samanich J, Zackai EH, Deardorff MA, Clark D, Allen JL, Dorsett D, Misulovin Z, Komata M, Bando M, Kaur M, Katou Y, Shirahige K*, Krantz ID*.
  • Journal Title: Nature Genetics Volume: 47 Issue: 4 Pages: 338-338
  • DOI: 10.1038/ng.3229
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chromatin immunoprecipitation protocol for mammalian cells. (2014)
  • Author(s): Komata M, Katou Y, Tanaka H, Nakato R, Shirahige K, Bando M.
  • Journal Title: Methods Mol Biol. Volume: 1164 Pages: 33-38
  • DOI: 10.1007/978-1-4939-0805-9_4
  • ISBN: 9781493908042, 9781493908059
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Design, Synthesis, and Biological Activity of NCC149 Derivatives as Histone Deacetylase 8-Selective Inhibitors. (2014)
  • Author(s): Suzuki T, Muto N, Bando M, Itoh Y, Masaki A, Ri M, Ota Y, Nakagawa H, Iida S, Shirahige K, Miyata N.
  • Journal Title: ChemMedChem. Volume: 9 Issue: 3 Pages: 657-664
  • DOI: 10.1002/cmdc.201300414
  • Peer Reviewed
• [Journal Article] Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells. (2014)
  • Author(s): Gallego-Paez LM, Tanaka H, Bando M, Takahashi M, Nozaki N, Nakato R, Shirahige K*, Hirota T*.(Shared Corresponding Authors)
  • Journal Title: Mol Biol Cell. Volume: 27 Issue: 2 Pages: 2736-2748
  • DOI: 10.1091/mbc.e13-01-0020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance. (2014)
  • Author(s): Kaiser FJ, Ansari M, Braunholz D, et al
  • Journal Title: Hum Mol Genet. Volume: Jan Issue: 11 Pages: 1-13
  • DOI: 10.1093/hmg/ddu002
  • Peer Reviewed
• [Journal Article] Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. (2013)
  • Author(s): Kon A, Yoshida K
  • Journal Title: Nature Genet. Volume: 45 Issue: 10 Pages: 1232-1237
  • DOI: 10.1038/ng.2731
  • Peer Reviewed
• [Presentation] The role of cohesin and cohesin loader in transcripitional regulation (2015)
  • Author(s): Masashige Bando, Ryuichiro Nakato, Kazuhiro Akiyama, Hiroshi Tanaka, Yuki Katou, Katsuhiko Shirahige
  • Organizer: EMBO workshop ‘SMC proteins’
  • Place of Presentation: siena, Italy
  • Year and Date: 2015-05-12
  • Int'l Joint Research
• [Presentation] The role of Cohesin loader in transcripitional regulation (2014)
  • Author(s): Masashige Bando, Ryuichiro Nakato, Kazuhiro Akiyama, Hiroshi Tanaka, Yuki Katou, Katsuhiko Shirahige
  • Organizer: The 4D nucleosome 2014
  • Place of Presentation: 広島
  • Year and Date: 2014-12-17 – 2014-12-20
• [Presentation] 転写調節におけるコヒーシンローダーの機能解析 (2014)
  • Author(s): 坂東優篤、中戸隆一郎、秋山和弘、田中博志、加藤由起、白髭克彦
  • Organizer: 日本分子生物学会第３８年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-29 – 2014-12-02
• [Presentation] Interacting networks of cohesin and cohesin loader (2013)
  • Author(s): Makiko Komata, Katsuhiko Shirahige,Masashige Bando
  • Organizer: Cohesin Biology and the Cohesinopathies
  • Place of Presentation: Siena, Italy
• [Book] 細胞工学 染色体工学Update 2015 vol.34.11月 (2015)
  • Author(s): 坂東優篤、秋山和弘、白髭克彦
  • Total Pages: 5
  • Publisher: 細胞工学 学研メディカル秀潤社