Establishment mechanism of 3D chromatin structure

• Project/Area Number: 18K14620
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nakamura Ryohei 東京大学, 大学院理学系研究科(理学部), 助教 (30756458)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: クロマチン３次元構造 / 発生 / リプログラミング / クロマチン / コヒーシン / メダカ

Outline of Final Research Achievements

Immediately after fertilization, chromosomes undergo reprogramming, resetting the chromatin modifications of sperms and oocytes into patterns that control totipotency. During this process, three-dimensional structure of the genome also dramatically changes, but the molecular mechanisms involved are unknown. Factors such as cohesin and CTCF are thought to play a central role in the regulation of the three-dimensional structure of the genome, but the dynamics of these factors in fertilized eggs have not been analyzed due to technical problems such as low cell numbers. In this study, we analyzed the dynamics of CTCF binding on chromatin in early embryos of medaka fish. As a result, we found that CTCF is specifically bound on chromatin even before its three-dimensional structure is established.

Academic Significance and Societal Importance of the Research Achievements

クロマチンのリプログラミングは、発生の最も初期に起こる分化多能性を確立する上で重要なプロセスである。この過程においてDNAメチル化やヒストン修飾などと共にゲノムの３次元構造も大きく変化するが、その分子メカニズムは不明である。特に、ゲノム３次元構造は転写制御に大きく関与していると考えられており、本研究で得られた初期胚におけるCTCFの動態解析の結果は、発生過程における遺伝子発現制御機構を理解する上で必要不可欠である。さらに、リプログラミングを制御する分子メカニズムの理解は再生医療などへの応用も期待される。

Research Products

• [Journal Article] CTCF looping is established during gastrulation in medaka embryos (2021)
  • Author(s): Ryohei Nakamura, Yuichi Motai, Masahiko Kumagai, Candice L. Wike, Haruyo Nishiyama, Yoichiro Nakatani, Neva C. Durand, Kaori Kondo, Takashi Kondo, Tatsuya Tsukahara, Atsuko Shimada, Bradley R. Cairns, Erez Lieberman Aiden, Shinichi Morishita, and Hiroyuki Takeda
  • Journal Title: Genome Research Volume: 31
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Chromatin architecture transitions from zebrafish sperm through early embryogenesis (2021)
  • Author(s): Candice L Wike, Yixuan Guo, Mengyao Tan, Ryohei Nakamura, Dana Shaw, Noelia Diaz, Aneasha F. Whittaker-Tademy, Neva C. Durand, Erez Lieberman Aiden, Juanma Vaquerizas , David Grunwald, Hiroyuki Takeda, and Bradley R. Cairns
  • Journal Title: Genome Research Volume: 31
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Nearly Complete Genome of Ciona intestinalis Type A (C.?robusta) Reveals the Contribution of Inversion to Chromosomal Evolution in the Genus Ciona (2019)
  • Author(s): Satou Yutaka、Nakamura Ryohei、Yu Deli、Yoshida Reiko、Hamada Mayuko、Fujie Manabu、Hisata Kanako、Takeda Hiroyuki、Satoh Noriyuki
  • Journal Title: Genome Biology and Evolution Volume: 11 Issue: 11 Pages: 3144-3157
  • DOI: 10.1093/gbe/evz228
  • NAID: 120006770371
• [Journal Article] Targeted in vivo epigenome editing of H3K27me3 (2019)
  • Author(s): Fukushima Hiroto S.、Takeda Hiroyuki、Nakamura Ryohei
  • Journal Title: Epigenetics & Chromatin Volume: 12 Issue: 1
  • DOI: 10.1186/s13072-019-0263-z
  • Peer Reviewed / Open Access
• [Presentation] Establishment of the three-dimensional genome structure during medaka fish development (2019)
  • Author(s): Ryohei Nakamura
  • Organizer: Keystone Symposia, 3D Genome: Gene Regulation and Disease
  • Int'l Joint Research