molecular mechanisms of genomic rejuvenation during preimplantation development

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293345
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: HAMATANI TOSHIO 慶應義塾大学, 医学部, 講師 (60265882)
• Co-Investigator(Kenkyū-buntansha): AKUTSU HIDENORI 国立成育医療研究センター, 生殖・細胞医療研究部, 部長 (50347225) ; HATA KENICHIRO 国立成育医療研究センター, 周産期病態研究部, 部長 (60360335) ; TSUMURA HIDEKI 国立成育医療研究センター, 実験動物管理室, 室長 (20180052)
• Co-Investigator(Renkei-kenkyūsha): UMEZAWA AKIHIRO 国立成育医療研究センター, 生殖・細胞医療研究部, 部長 (70213486)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 生殖医学

Outline of Final Research Achievements

This study found novel mouse genes (e.g. Kzpi encoding KRAB zinc-finger and Zfpi encoding SCAN-zinc finger) exclusively and zygotically expressed in preimplantation embryos and ES cells. Kzpi-deficient mice showed smaller litter sizes. Interestingly, most imprinted genes were down regulated and the methylation levels of differentially methylated regions (DMRs) were decreased in homozygous ES cells. Kzpi was thus suggested to maintain DMRs against genome-wide demethylation in preimplantation embryos. However, transgenerational phenotypic attenuation of Kzpi-deficient mice was observed: normal methylation patterns of DMRs in Kzpi-deficient blastocyst and ES cells. Zfpi-deficient mice did not show any phenotype, but karyotype analysis revealed chromosomal gaps. Kzpi-deficient ES cells generated a teratoma composed of all the three-germ layer, but gave rise to embryonal carcinoma.

Free Research Field

医歯薬学