Genome-Wide Dynamic Profiling of Histone Methylation during Nuclear Transfer-Mediated Porcine Somatic Cell Reprogramming.
Genome-Wide Dynamic Profiling of Histone Methylation during Nuclear Transfer-Mediated Porcine Somatic Cell Reprogramming.
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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
DOI：
10.1371/journal.pone.0144897
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Cao Z;Li Y;Chen Z;Wang H;Zhang M;Zhou N;Wu R;Ling Y;Fang F;Li N;Zhang Y
猪体细胞核移植（SCNT）胚胎发育效率低的主要原因是早期胚胎表观遗传重编程不完善。然而，在猪SCNT胚胎早期发育过程中，参与表观遗传重编程进展的组蛋白甲基化的动态表达模式仍然未知。在这项研究中，我们表征并比较了多种组蛋白甲基化标记物的表达模式，包括转录抑制性甲基化标记物。（H3 K9 me 2、H3 K9 me 3、H3 K27 me 2、H3 K27 me 3、H4 K20 me 2和H4 K20 me 3）和活性修饰H3 K4 me 2、H3 K4 me 3、H3 K36 me 2、H3 K36 me 3、H3 K79 me 2和H3 K79 me 3在不同发育阶段的SCNT早期胚胎与体外受精（IVF）胚胎中的表达差异。结果表明，H3 K9 me 2、H3 K9 me 3和H4 K20 me 3在1- 4细胞期SCNT胚胎中的表达水平显著高于IVF胚胎。在SCNT囊胚中，我们还检测到H3 K9 me 2在内细胞团（ICM）和滋养外胚层（TE）之间的对称分布模式。H3 K9 me 2在两个谱系中的表达水平从SCNT扩张囊胚开始显著高于IVF对应物。H4 K20 me 2在桑椹胚至囊胚期SCNT胚胎中的表达水平显著低于IVF胚胎。然而，没有异常的动态重编程H3 K27 me 2/3发生在早期发育阶段的SCNT胚胎。H3 K4 me 3在4-细胞期SCNT胚胎中的表达高于IVF胚胎。H3 K4 me 2在8-细胞期至囊胚期的SCNT胚胎中的表达低于IVF胚胎。其他活跃的组蛋白甲基化标记物的动态模式在SCNT和IVF胚胎之间是相似的。总之，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。
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.