Functional analysis of core histones using genome-modified cells

• Project/Area Number: 18K06186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: University of Miyazaki
• Principal Investigator: Takami Yasunari 宮崎大学, 医学部, 准教授 (80236356)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ヒストン / クロマチン / エピジェネティクス / エピゲノム / エピジェネティックス / コアヒストン

Outline of Final Research Achievements

Using histone H1-null mutant cells, we found that the apoptotic chromatin condensation was decreased in the null mutant cells and that the chromatin in the nuclei prepared from the live null mutant cells had the high accessibility of DNases and transposase, suggesting that linker histone H1 is the apoptotic chromatin condensation factor and that the loss of histone H1 generates open chromatin in live cells. Furthermore, using the deterministic lateral displacement microfluidic device that can separate cells according to cell stiffness, we found that the null mutant cells are more flexible than DT40 cells, suggesting that the cell stiffness is also determined by histone H1.

Academic Significance and Societal Importance of the Research Achievements

クロマチン制御の研究のほとんどは、ヒストンにトランスに働きかけるタンパク質群の解析に偏っていた。ヒストン分子を遺伝学的に機能解析する研究は変異株樹立の困難さからほとんど行われていない。本研究で得られたヒストンH１の新規生理機能に関する知見は将来的に、エピジェネティクスの制御を対象とした新規薬剤開発研究への応用が期待される。