Over expression of Uhrf1 to regulate DNA methylation in PGCs

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19295
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Nara Medical University
• Principal Investigator: Kurimoto Kazuki 奈良県立医科大学, 医学部, 教授 (20415152)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: PGC / エピゲノム / リプログラミング / 始原生殖細胞 / DNAメチル化

Outline of Final Research Achievements

It is believed that the only genetic information transmitted from parents to offspring is usually DNA sequence information. However, it has been reported that environmental and other influences on the fetus can be passed on to the next generation. Since DNA is known to undergo methylation modification, it is thought to be a promising source of information other than base sequences to be transmitted to the next generation. Primordial germ cells (PGCs) undergo erasure of DNA methylation, before sperm ad oocytes start to develop. This project aim to make a method to manipulate expression level of UHRF1 in PGCs; UHRF1 is a protein involved in maintenance of DNA methylation by recruiting DNMT1 to the replication foci.

Free Research Field

発生生物学・ゲノム科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではUhrf1を過剰発現させるES細胞から始原生殖細胞を誘導し、その性状解析を行った。その結果、遺伝子発現の過剰発現が起きていることがわかった。このことは、子孫に受け継がれ、遺伝情報の担い手である生殖細胞のゲノムDNAに対して直接化学修飾を操作することができる可能性を示唆している。一方で、精密な発現誘導の制御には、この実験系のさらなる改良が必要なことも示唆された。