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Paternal genome rescues mouse preimplantation embryo development in the absence of maternally-recruited EZH2 activity

文献类型: 外文期刊

作者: Wang, Huili 1 ; Paulson, Erika E. 3 ; Ma, Libing 4 ; Ross, Pablo J. 3 ; Schultz, Richard M. 2 ;

作者机构: 1.Jiangsu Acad Agr Sci, Inst Anim Sci, Nanjing, Jiangsu, Peoples R China

2.Univ Calif Davis, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA

3.Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA

4.Inner Mongolia Univ Sci & Technol, Sch Life Sci & Technol, Baotou, Peoples R China

5.Univ Penn, Dept Biol, Philadelphia, PA 19104 USA

关键词: EZH2; histone methylation; preimplantation mouse embryo; gene expression

期刊名称:EPIGENETICS ( 影响因子:4.528; 五年影响因子:5.22 )

ISSN: 1559-2294

年卷期: 2019 年 14 卷 1 期

页码:

收录情况: SCI

摘要: Enhancer of zeste homolog 2 (EZH2), a component of the PRC2 complex, trimethylates H3K27, a transcriptionally repressive histone mark. EZH2 is encoded by a dormant maternal mRNA and inhibiting the maturation-associated increase in EZH2 activity using either a combined siRNA/morpholino approach or a small molecule inhibitor (GSK343) inhibits development of diploidized parthenotes to the blastocyst stage but not inseminated eggs, with longer GSK343 treatments leading to progressively greater inhibition of development. GSK343 treatment also results in a decrease in H3K27me3 and a decrease in global transcription in 2-cell parthenotes but not 2-cell embryos derived from inseminated eggs. RNA-sequencing revealed the relative abundance of similar to 100 zygotically-expressed transcripts is decreased by GSK treatment in parthenotes, but not in embryos, with many of the affected transcripts encoding proteins involved in transcription. A previous study found that parthenotes deficient in maternal Ezh2 readily develop to the blastocyst stage. To reconcile these differences we propose that the H3K27me3 state present in the zygote needs to be faithfully propagated following DNA replication in at least one pronucleus, otherwise development is compromised.

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