Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development
| Autor: | Yi Zhang, Xiaoji Wu, Atsuo Ogura, Kumiko Iwabuchi, Falong Lu, Huihan Wang, William H. Press, Li Shen, Shogo Matoba, Lin Yang, Jeannie T. Lee, Kimiko Inoue, Lan Jiang |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Nuclear Transfer Techniques Mice Inbred Strains Biology Article Histones Genomic Imprinting Mice 03 medical and health sciences Genetics Animals Embryo Implantation Epigenetics Imprinting (psychology) Mice Knockout Embryo Cell Biology Embryo Mammalian Cell biology 030104 developmental biology DNA methylation Molecular Medicine Somatic cell nuclear transfer Female XIST Genomic imprinting Reprogramming |
| Zdroj: | Cell Stem Cell. 23:343-354.e5 |
| ISSN: | 1934-5909 |
| DOI: | 10.1016/j.stem.2018.06.008 |
| Popis: | Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), although the live birth rate is relatively low. Recent studies have identified H3K9me3 in donor cells and abnormal Xist activation as epigenetic barriers that impede SCNT. Here we overcome these barriers using a combination of Xist knockout donor cells and overexpression of Kdm4 to achieve more than 20% efficiency of mouse SCNT. However, post-implantation defects and abnormal placentas were still observed, indicating that additional epigenetic barriers impede SCNT cloning. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified abnormally methylated regions in SCNT embryos despite successful global reprogramming of the methylome. Strikingly, allelic transcriptomic and ChIP-seq analyses of pre-implantation SCNT embryos revealed complete loss of H3K27me3 imprinting, which may account for the postnatal developmental defects observed in SCNT embryos. Together, these results provide an efficient method for mouse cloning while paving the way for further improving SCNT efficiency. |
| Databáze: | OpenAIRE |
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