• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of an epigenetic hierarchy mediated by CXXC proteins

Research Project

Project/Area Number 15H05602
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Genetics/Chromosome dynamics
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

ITO SHINSUKE  国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (50612115)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsエピジェネティクス / CpGアイランド / 遺伝子発現抑制 / ポリコーム / ユビキチン / 転写抑制 / 転写制御 / ゲノム / 発現制御 / CGI / CXXC
Outline of Final Research Achievements

The majority of mammalian gene promoters are associated with specialized genomic regions called CpG islands (CGI) that contribute to regulation of gene expression by attracting specific histone modifying enzymes. However, the precise mechanisms by which how CXXC domain-containing proteins, CXXC1 and KDM2B specifically recognize their target CGIs remain poorly understood. Therefore, in this project, we aim to understand the detailed mechanisms to establish epigenetic modifications at specific loci.Here, by using biochemical approach combined with a mice genetic study, we demonstrated CXXC1 and KDM2B specifically recruit associated complex and induce epigenetic modifications. We also revealed Polycomb-proteasome axis could play a critical role in specification of recruitment of CXXC-associated complexes. Therefore, ubiquitin-proteasome system is involves in polycomb-mediated transcriptional regulation and could serve as a gatekeeper for ensuring a proper epigenetic landscape of CGI.

Academic Significance and Societal Importance of the Research Achievements

エピジェネティック修飾は、個体発生 ・分化の過程において時空間的に厳格な遺伝子発現制御を行う上で重要な役割を果たしている。このエピジェネティック修飾は、その重要さ故に、エピジェネティック修飾の破綻は、様々な疾患の発症に繋がるため、エピジェネティック修飾が如何に導入されるかを詳細に理解することは極めて重要である。とりわけ、CpGアイランドのエピジェネティック修飾の異常が様々な疾患やがんにて報告されている。したがって、本研究成果は、エピジェネティック修飾の忠実に導入するメカニズムの一端を明らかにするものであり、その異常が疾患発症の原因になる可能性をもつとかんがえる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (14 results)

All 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Int'l Joint Research] オックスフォード大学(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Oxford(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] オックスフォード大学(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Synergy between Variant PRC1 Complexes Defines Polycomb-Mediated Gene Repression2019

    • Author(s)
      Fursova NA, Blackledge NP, Nakayama M, Ito S, Koseki Y, Farcas AM, King HW, Koseki H, Klose RJ.
    • Journal Title

      Molecular Cell

      Volume: 印刷中 Issue: 5 Pages: 1020-1036

    • DOI

      10.1016/j.molcel.2019.03.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities.2018

    • Author(s)
      Conway E, Jerman E, Healy E, Ito S, Holoch D, Oliviero G, Deevy O, Glancy E, Fitzpatrick DJ, Mucha M, Watson A, Rice AM, Chammas P, Huang C, Pratt-Kelly I, Koseki Y, Nakayama M, Ishikura T, Streubel G, Wynne K, Hokamp K, McLysaght A, Ciferri C, Di Croce L, Cagney G, Margueron R, Koseki H, Bracken AP.
    • Journal Title

      Mol Cell.

      Volume: 70 Issue: 3 Pages: 408-421

    • DOI

      10.1016/j.molcel.2018.03.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.2017

    • Author(s)
      Brown DA, Di Cerbo V, Feldmann A, Ahn J, Ito S, Blackledge NP, Nakayama M, McClellan M, Dimitrova E, Turberfield AH, Long HK, King HW, Kriaucionis S, Schermelleh L, Kutateladze T, Koseki H, Klose RJ.
    • Journal Title

      Cell Rep

      Volume: 20 Issue: 10 Pages: 2313-2327

    • DOI

      10.1016/j.celrep.2017.08.030

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes.2017

    • Author(s)
      Endoh M, Endo TA, Shinga J, Hayashi K, Farcas A, Ma KW, Ito S, Sharif J, Endoh T, Onaga N, Nakayama M, Ishikura T, Masui O, Kessler BM, Suda T, Ohara O, Okuda A, Klose RJ, Koseki H.
    • Journal Title

      Elife

      Volume: 6 Pages: 27970-27970

    • DOI

      10.7554/elife.21064

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polycomb in transcriptional phase transition of developmental genes2016

    • Author(s)
      Kondo, T., Koseki, H. and Ito, S.
    • Journal Title

      Trends Biochem. Sci.

      Volume: 41 Issue: 1 Pages: 9-19

    • DOI

      10.1016/j.tibs.2015.11.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Epigenetic modifications in DNA could mimic oxidative DNA damage: A double-edged sword.2015

    • Author(s)
      Ito S, Kuraoka I
    • Journal Title

      DNA Repair

      Volume: 32 Pages: 52-57

    • DOI

      10.1016/j.dnarep.2015.04.013

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] ポリコーム複合体PRC1.1によるCpGアイランドのエピゲノム制御2019

    • Author(s)
      伊藤伸介
    • Organizer
      第2回ユビキチン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポリコーム複合体PRC1.1によるCpGアイランドのエピゲノム制御2018

    • Author(s)
      伊藤伸介
    • Organizer
      第41回日本分子生物学会年会ワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] Role of CXXC1 in transcriptional regulation and cell-fate decision2016

    • Author(s)
      Shinsuke Ito, Marika Shibata, Hiroki Sugishita, Takashi Kondo, and Haruhiko Koseki
    • Organizer
      EMBL Conference: Transcription and Chromatin
    • Place of Presentation
      EMBLハイデルベルグ、ドイツ
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of CXXC1 in transcriptional regulation and cell-fate decision2016

    • Author(s)
      Shinsuke Ito, Marika Shibata, Takashi Kondo and Haruhiko Koseki
    • Organizer
      Kick-off symposium in Nagoya City University 2016
    • Place of Presentation
      Nagoya City University Hospital
    • Year and Date
      2016-02-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] 細胞工学、ポリコーム複合体によるエピゲノム制御2015

    • Author(s)
      伊藤伸介, 古関明彦
    • Total Pages
      5
    • Publisher
      秀潤社
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2022-08-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi