Mechanism of DNA structures regulated by G-quadruplex binding protein

2016 Fiscal Year Final Research Report

• Project/Area Number: 26410176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Shizuoka University
• Principal Investigator: Oyoshi Takanori 静岡大学, 理学部, 准教授 (80406529)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: グアニン四重鎖 / テロメア / 核酸結合タンパク質 / ヌクレオソーム / エピジェネティクス / ガン遺伝子 / ヒストン修飾

Outline of Final Research Achievements

G-qudruplex DNA and RNA are thought as components of genome DNA and transcribed RNA, respectively. But the biological significance of their G-quadruplex formation is unknown. Compounds that selectively bind G-quadruplex DNA and RNA are useful toward understanding the functions of each G-quadruplex. Especially, human telomere DNA and telomeric repeat-containing RNA (TERRA) are integral telomere components. We report that engineered Arg-Gly-Gly repeat (RGG) domains of translocated in liposarcoma containing only Phe (RGGF) and Tyr (RGGY) specifically bind and stabilize the G-quadruplexes of telomere DNA and TERRA, respectively. Moreover, RGGF inhibits trimethylation of both histone H4 at lysine 20 and histone H3 at lysine 9 at telomeres, while RGGY inhibits only H3 trimethylation in living cells. These findings indicate that G-quadruplexes of telomere DNA and TERRA have distinct functions in telomere histone methylation.

Free Research Field

生物化学