Effect of epigenomic mutation on preimplantation development

• Project/Area Number: 26861350
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Fukuda Atsushi 国立研究開発法人国立成育医療研究センター, 細胞医療研究部, 研究員 (00638091)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 初期胚 / 生殖細胞 / エピジェネティクス / 生殖

Outline of Final Research Achievements

Using mouse embryos as model for studying the effect of epigenomic mutations on embryonic development, the embryos with alteration of epigenetic states were produced using mRNA overexpression and treatment of small molecule. These treatments caused maternal Xist derepression in preimplantation stages. Moreover, using these system, we demonstrated that the female lethality in Xist paternal deleted embryos could be rescued. These results provide new insight into reproductive medicine.

Research Products

• [Journal Article] Spatiotemporal dynamics of OCT4 protein localization during preimplantation development in mice (2016)
  • Author(s): Fukuda A, Mitani A, Miyashita T, Kobayashi H, Umezawa A, Akutsu H
  • Journal Title: Reproduction Volume: 152 Issue: 5 Pages: 417-30
  • DOI: 10.1530/rep-16-0277
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maintenance of Xist imprinting depends on chromatin condensation state and Rnf12 dosage in mice. (2016)
  • Author(s): Fukuda, A., Mitani, A., Miyashita, T., Sado, T., Umezawa, A., and *Akutsu, H.
  • Journal Title: PloS Genet. Volume: 12(10) Issue: 10 Pages: e1006375-e1006375
  • DOI: 10.1371/journal.pgen.1006375
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Imbalance between the expression dosages of X-chromosome and autosomal genes in mammalian oocytes (2015)
  • Author(s): Atsushi Fukuda, Motohiko Tanino, Ryo Matoba, Akihiro Umezawa, Hidenori Akutsu
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 14101-14101
  • DOI: 10.1038/srep14101
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Chromatin condensation of Xist genomic loci during oogenesis in mice (2015)
  • Author(s): Fukuda, A., Mitani, A., Miyashita, T., Umezawa, A., Akutsu, H
  • Journal Title: Development Volume: 142 Pages: 4049-4055
  • DOI: 10.1242/dev.127308
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice. (2014)
  • Author(s): Fukuda A, Tomikawa J, Miura T, Hata K, Nakabayashi K, Eggan K, Akutsu H, Umezawa A.
  • Journal Title: Nat Commun. Volume: 5 Issue: 1 Pages: 5464-5464
  • DOI: 10.1038/ncomms6464
  • Peer Reviewed / Open Access