Gene regulation system by ternary chemical modifications of DNA, histone, and osmolyte

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H03840
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Konan University
• Principal Investigator: MIYOSHI Daisuke 甲南大学, フロンティアサイエンス学部, 教授 (50388758)
• Co-Investigator(Kenkyū-buntansha): 川内 敬子 甲南大学, フロンティアサイエンス学部, 講師 (40434138)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オスモライト / ヒストン / 分子クラウディング / DNA / 熱力学

Outline of Final Research Achievements

In cell nucleus, DNA exists with histone proteins, which form nucleosome complex. Binding affinity between DNA and the histone proteins is one of the critical factors for epigenetic regulation of gene expression. Moreover, there are highly concentrated osomolytes inside cells, which may also affect the binding affinity of DNA with the histone proteins. Therefore, to elucidate the epigenetics, it is important to study combination effects of the epigenetic modifications on the histone proteins and on DNA, and osmolytes, on DNA structures and their thermodynamic stability.
In this project, we utilized peptides and synthetic polymers to mimic the histone tails, and TMAO and urea to mimic the osmolytes. It was found that histone-mimicking polymers drastically change DNA structures and thermodynamics. Moreover, it was found for the first time that TMAO directly binds and stabilizes DNA duplex at lower concentration, whereas it destabilizes it because of dehydration from DNA structure.

Free Research Field

生体関連化学