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核移植介导的猪体细胞重编程过程中组蛋白甲基化的全基因组动态分析

Genome-Wide Dynamic Profiling of Histone Methylation during Nuclear Transfer-Mediated Porcine Somatic Cell Reprogramming.

作者信息

Cao Zubing, Li Yunsheng, Chen Zhen, Wang Heng, Zhang Meiling, Zhou Naru, Wu Ronghua, Ling Yinghui, Fang Fugui, Li Ning, Zhang Yunhai

机构信息

Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei City, Anhui Province, China.

State Key Laboratory for Agrobiotechnology, College of Biological Science, China Agricultural University, Haidian District, Beijing, China.

出版信息

PLoS One. 2015 Dec 18;10(12):e0144897. doi: 10.1371/journal.pone.0144897. eCollection 2015.

Abstract

The low full-term developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos is mainly attributed to imperfect epigenetic reprogramming in the early embryos. However, dynamic expression patterns of histone methylation involved in epigenetic reprogramming progression during porcine SCNT embryo early development remain to be unknown. In this study, we characterized and compared the expression patterns of multiple histone methylation markers including transcriptionally repressive (H3K9me2, H3K9me3, H3K27me2, H3K27me3, H4K20me2 and H4K20me3) and active modifications (H3K4me2, H3K4me3, H3K36me2, H3K36me3, H3K79me2 and H3K79me3) in SCNT early embryos from different developmental stages with that from in vitro fertilization (IVF) counterparts. We found that the expression level of H3K9me2, H3K9me3 and H4K20me3 of SCNT embryos from 1-cell to 4-cell stages was significantly higher than that in the IVF embryos. We also detected a symmetric distribution pattern of H3K9me2 between inner cell mass (ICM) and trophectoderm (TE) in SCNT blastocysts. The expression level of H3K9me2 in both lineages from SCNT expanded blastocyst onwards was significantly higher than that in IVF counterparts. The expression level of H4K20me2 was significantly lower in SCNT embryos from morula to blastocyst stage compared with IVF embryos. However, no aberrant dynamic reprogramming of H3K27me2/3 occurred during early developmental stages of SCNT embryos. The expression of H3K4me3 was higher in SCNT embryos at 4-cell stage than that of IVF embryos. H3K4me2 expression in SCNT embryos from 8-cell stage to blastocyst stage was lower than that in the IVF embryos. Dynamic patterns of other active histone methylation markers were similar between SCNT and IVF embryos. Taken together, histone methylation exhibited developmentally stage-specific abnormal expression patterns in porcine SCNT early embryos.

摘要

猪体细胞核移植(SCNT)胚胎的足月发育效率较低,主要归因于早期胚胎中表观遗传重编程不完善。然而,猪SCNT胚胎早期发育过程中参与表观遗传重编程进程的组蛋白甲基化动态表达模式仍不清楚。在本研究中,我们对包括转录抑制性(H3K9me2、H3K9me3、H3K27me2、H3K27me3、H4K20me2和H4K20me3)和活性修饰(H3K4me2、H3K4me3、H3K36me2、H3K36me3、H3K79me2和H3K79me3)在内的多种组蛋白甲基化标记物在不同发育阶段的SCNT早期胚胎中的表达模式与体外受精(IVF)胚胎进行了表征和比较。我们发现,从1细胞到4细胞阶段的SCNT胚胎中H3K9me2、H3K9me3和H4K20me3的表达水平显著高于IVF胚胎。我们还检测到SCNT囊胚内细胞团(ICM)和滋养外胚层(TE)之间H3K9me2的对称分布模式。从SCNT扩张囊胚开始,两个谱系中H3K9me2的表达水平均显著高于IVF胚胎。与IVF胚胎相比,桑椹胚到囊胚阶段的SCNT胚胎中H4K20me2的表达水平显著降低。然而,在SCNT胚胎的早期发育阶段未发生H3K27me2/3的异常动态重编程。4细胞阶段的SCNT胚胎中H3K4me3的表达高于IVF胚胎。从8细胞阶段到囊胚阶段的SCNT胚胎中H3K4me2的表达低于IVF胚胎。SCNT和IVF胚胎之间其他活性组蛋白甲基化标记物的动态模式相似。综上所述,组蛋白甲基化在猪SCNT早期胚胎中表现出发育阶段特异性的异常表达模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a35/4687693/8d25f6e8de10/pone.0144897.g001.jpg

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