Erasure mechanisms of parental imprints during primordial germ cell development in mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 24613004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: epigenetics
• Research Institution: Tottori University
• Principal Investigator: TADA Masako 鳥取大学, 染色体工学研究センター, 教授 (10524910)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: DNAメチル化 / 5-ヒドロキシメチル化 / ES細胞 / クロマチン / リプログラミング / 始原生殖細胞

Outline of Final Research Achievements

DNA cytosine methylation (5mC) is involved in important regulatory mechanisms of gene expression and development in mammals. Genome-wide DNA demethylation occurs in preimplantation embryos and primordial germ cells (PGCs) during mouse embryonic development. Although erasure of the DNA methylation imprints never occurs during embryonic reprogramming, it occurs in PGCs. At the same time, PGC genomes return to the default state. By comparing DNA modification profiles of mouse embryonic stem cells (ESCs) with those of ESC-derived PGCs, we tried to examine which factors excluding Yamanaka’s 4 factors were primarily responsible for the erasure of parental imprints. In ESC-derived PGCs, we found an extensive conversion of 5mC to 5-hydroximethylation (5hmC) at condensed heterochromatic regions, but it was not detected in undifferentiated ESCs. Therefore, decondensation of heterochromatin may initiate the further reprogramming during PGC development, leading to the erasure imprints.

Free Research Field

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