Epigenetic mechanisms regulating the maintenance and differentiation of neural stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24300136
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: HITOSHI Seiji 滋賀医科大学, 医学部, 教授 (70300895)
• Co-Investigator(Renkei-kenkyūsha): IKENAKA Kazuhiro 生理学研究所, 分子生理研究系, 教授 (00144527)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 神経幹細胞 / エピゲノム / DNAメチル化 / ヒストン修飾

Outline of Final Research Achievements

We have investigated the function of Gcm1 and 2, which catalyze the active demethylation of DNA, and Rnf20, a histone H2B ubiquitylation factor, in the maintenance and differentiation of neural precursor cells. We found that Gcm genes upregulate the expression of GFAP, through the demethylation of its promoter DNA. We also revealed that Rnf20 is expressed in most but not all neural precursor cells and is indispensable for the cell cycle progression and differentiation. The knockdown of Rnf20 in neural precursor cells lengthened their cell cycle through the action of p57kip2 and Cdk2. Furthermore, we demonstrate that Rnf20 controls differentiation of neural precursor cells through the promotion of Fezf1 and Fezf2 expression, which suppress the Notch signaling pathway. Our data suggest that Rnf20 could be a bifunctional gene that regulates both the differentiation status and cell cycle length of neural precursor cells.

Free Research Field

神経科学、幹細胞生物学