Understanding of non-genome replication during hematopoietic cell differentiation

2023 Fiscal Year Final Research Report

• Project Area: Mechanisms underlying replication of non-genomic codes that mediate plasticity and robustness for cellular inheritance
• Project/Area Number: 19H05747
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Taniuchi Ichiro 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (20284573)
• Co-Investigator(Kenkyū-buntansha): 河本 宏 京都大学, 医生物学研究所, 教授 (00343228)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: 非ゲノム複製 / T細胞

Outline of Final Research Achievements

Inheritance of non-genomic information is essential for inheritance of cellular phenotype. On the other hand, such non-genomic information has plasticity and can be re-wired, thereby it functions as the basic principle for generating diverse cell types. Elucidation of the mechanisms that control the modification and precise replication of non-genomic information is an important issue in biology. In this research project, we have designed researches to elucidate the mechanisms of replication of non-genomic information, by using hematopoietic cell differentiation as a model. We identified Dot1L, Runx3, and Ambra1 as a molecule essential for the maintenance of Cd8 gene expression by screening gRNA libraries.
We established the in vivo AID2 system in mice for drug-inducible, temporal degradation of target proteins as a new research method for identification and functional analysis of nuclear proteins involved in the formation and maintenance of higher-order chromatin structures.

Free Research Field

分子免疫学

Academic Significance and Societal Importance of the Research Achievements

鐘巻との共同開発した薬剤依存的に一過性に標的タンパク質をマウス生体内で分解するマウス生体内AID2法は応用範囲が広く、医学や薬学研究に革新的変化をもたらす新規実験手法と言える。