Establishment mechanism of 3D chromatin structure

2021 Fiscal Year Final Research Report

• 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
• Keywords: クロマチン３次元構造 / 発生 / リプログラミング

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.

Free Research Field

エピジェネティクス

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。