Elucidation of cell cycle-dependent regulation for centromere chromatin establishment, which is essential for the kinetochore formation in vertebrate cells.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Genetics/Chromosome dynamics
• Research Institution: Osaka University
• Principal Investigator: Hori Tetsuya 大阪大学, 生命機能研究科, 准教授 (70550078)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: セントロメア / ヒストン修飾 / エピジェネティックス / 細胞周期 / クロマチン

Outline of Final Research Achievements

We demonstrated that KNL2, a member of the Mis18 complex, was essential for the stable inheritance of the centromere position at G1-phase through direct binding to CENP-A nucleosome to deposit new CENP-A in chicken DT40 cells. We revealed the 3D architecture of the interphase genome, including the centromeres by systematic 4C-seq analysis using DT40 cell lines. Based on structural and genetic analyses, we conclude that a CENP-A-mediated structural polymorphism facilitated the preferential H4K20 monomethylation in centromeric nucleosomes. These findings may provide insight into developing an anti-cancer drug utilizing chromatin modulation.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

遺伝情報の継承に重要な、細胞核内のセントロメアのクロマチンの形成の仕組みと、その安定維持を保証するメカニズムの一端を明らかにした。これら成果は、細胞の遺伝情報の伝播の仕組みを解明する鍵となる知見として期待される。さらに将来的には、これら成果を活用した抗がん剤などの新規薬剤開発研究への応用が期待される。