Chromatin reprogramming induces functional switching of DNA methylation enzyme

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Toho University (2017); Tottori University (2015-2016)
• Principal Investigator: TADA Masako 東邦大学, 理学部, 教授 (10524910)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: エピジェネティクス / DNAメチル化 / ES細胞 / クロマチン / 胚発生 / 細胞分化 / リプログラミング / Dnmt

Outline of Final Research Achievements

Accurate control of DNA methylation (5mC) is essential for mammalian embryogenic development. ES cells lacking all three types of DNA methyltransferases, de novo-type Dnmt3a and Dnmt3b and maintenance-type Dnmt1 can proliferate, but die immediately after cell differentiation. When Dnmt1 was expressed in the TKO ESCs, the TKO+1 ESCs became possible to differentiate. The differentiated cell genomes became gradually methylated, and Tet enzyme-mediated oxidation products of 5mC were also detected. DNA methylation occurred even in the undifferentiated state when compounds capable of chromatin activation were added to the cell culture medium. These results indicate that Dnmt1 possesses de novo DNA methylation activity as an innate function that appears only when genomes become extensively reprogrammed.

Free Research Field

エピジェネティクス