Generation of sex chromosome linked histone demethylase activity-converted mice and their effect on sex differentiation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22369
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Iwamori Naoki 九州大学, 農学研究院, 准教授 (70647362)
• Co-Investigator(Kenkyū-buntansha): 岩森 督子 九州大学, 医学研究院, 助教 (10711509)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 性決定 / 性染色体 / ヒストン脱メチル化酵素 / ゲノム編集 / UTX / UTY / 性差

Outline of Final Research Achievements

UTX and UTY are H3K27 demethylases encoded on sex chromosomes. Since there is a large difference in their demethylase activity between UTX and UTY, the aim of this study is that whether the difference in demethylase activity is involved in sex determination or not is determined by conversion of H3K27 demethylase activity of male to the female level and vice versa. By referring to the amino acid sequences and crystal structures of UTX and UTY, multiple amino acid mutants which could convert UTX activity to UTY level (UTX ↓) and UTY activity to UTX level (UTY ↑) were prepared. best amino acid mutants were identified by evaluation using cultured cells. Then, although mice with the identified amino acid mutations were prepared by genome editing, no sex conversion was observed in both females with UTX ↓ and males with UTY ↑.

Free Research Field

幹細胞生物学、生殖生物学

Academic Significance and Societal Importance of the Research Achievements

性は性染色体の遺伝的性で決定され、生殖線のみならず脳など様々な組織で性差が現れる。近年、LGBTなどの性の多様性が広く認識されるようになり、性差の制御にも多様性、連続性があるという考えが広まりつつある。本研究で対象とするUTXとUTYは活性が異なることから性差を構築する候補として考えられる。本研究結果によりUTX/UTYが雌雄の性決定に関わりがない可能性が高くなったことから、実際にUTX/UTY変異マウスが組織レベル、細胞レベルでの性差構築を解析する有用なツールとなることが示された。