TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos.
TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos.
复制标题
DOI：
10.1016/j.stemcr.2021.09.012
复制
发表时间：
2021-11-09
影响因子：
5.9
通讯作者：
Miao YL
中科院分区：
文献类型：
--
作者：
Liu X;Chen L;Wang T;Zhou J;Li Z;Bu G;Zhang J;Yin S;Wu D;Dou C;Xu T;He H;Zhu W;Yu L;Liu Z;Zhang X;Chen ZX;Miao YL
体细胞核移植克隆猪在母体向合子的转化过程中经常发生不完全的表观遗传重构，导致胚胎在着床前大量丢失。在这里，我们在猪SCNT胚胎中生成了第一个全基因组蛋白甲基化景观。过量的H3K9me3和H3K27me3，而不是H3K4me3，观察到在基因组区域与不忠实的胚胎基因组激活和供体细胞特异性基因沉默。H3K9去甲基化酶KDM4A和H3K27me3抑制剂GSK126的组合能够消除这些表观遗传障碍并恢复SCNT胚胎中的整体转录组。更重要的是，胸腺嘧啶DNA糖基化酶（TDG）被定义为猪特异性核重编程的表观遗传调节因子，其不被H3K9me3和H3K27me3去除重新激活。联合治疗和瞬时TDG过表达都促进了DNA去甲基化，提高了SCNT胚胎的囊胚形成率，从而为提高基因组编辑猪的克隆效率提供了有价值的方法，用于农业和生物医学目的。猪SCNT胚胎中重编程抗性基因和区域的鉴定H3K9me3和H3K27me3富含重编程抗性基因和区域通过KDM4A和GSK126去除H3K9me3和H3K27me3促进核重编程瞬时TDG过表达促进DNA去甲基化并改善重编程在这篇文章中，Miao及其同事表明，H3K9me3和H3K27me3是猪SCNT介导的重编程的表观遗传障碍。通过KDM4A和GSK126去除这些修饰改善了SCNT胚胎发育，但在胚胎基因组激活期间不会重新激活TDG。同时，瞬时TDG过表达促进DNA去甲基化，也促进了猪SCNT胚胎发育。
Pig cloning by somatic cell nuclear transfer (SCNT) frequently undergoes incomplete epigenetic remodeling during the maternal-to-zygotic transition, which leads to a significant embryonic loss before implantation. Here, we generated the first genome-wide landscapes of histone methylation in pig SCNT embryos. Excessive H3K9me3 and H3K27me3, but not H3K4me3, were observed in the genomic regions with unfaithful embryonic genome activation and donor-cell-specific gene silencing. A combination of H3K9 demethylase KDM4A and GSK126, an inhibitor of H3K27me3 writer, were able to remove these epigenetic barriers and restore the global transcriptome in SCNT embryos. More importantly, thymine DNA glycosylase (TDG) was defined as a pig-specific epigenetic regulator for nuclear reprogramming, which was not reactivated by H3K9me3 and H3K27me3 removal. Both combined treatment and transient TDG overexpression promoted DNA demethylation and enhanced the blastocyst-forming rates of SCNT embryos, thus offering valuable methods to increase the cloning efficiency of genome-edited pigs for agricultural and biomedical purposes. Identification of reprogramming-resistant genes and regions in porcine SCNT embryos H3K9me3 and H3K27me3 are enriched in reprogramming-resistant genes and regions Removing H3K9me3 and H3K27me3 by KDM4A and GSK126 facilitates nuclear reprogramming Transient TDG overexpression promotes DNA demethylation and improves reprogramming In this article, Miao and colleagues show that H3K9me3 and H3K27me3 are epigenetic barriers to porcine SCNT-mediated reprogramming. Removal of these modifications by KDM4A and GSK126 improves SCNT embryonic development, but does not reactivate TDG during embryonic genome activation. Meanwhile, transient TDG overexpression promotes DNA demethylation and also improves SCNT embryonic development in pigs.
登录
查看更多内容
影响因子：
23.9
作者：
Hörmanseder E;Simeone A;Allen GE;Bradshaw CR;Figlmüller M;Gurdon J;Jullien J
通讯作者：
Jullien J
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
影响因子：
3.7
作者：
Cao Z;Li Y;Chen Z;Wang H;Zhang M;Zhou N;Wu R;Ling Y;Fang F;Li N;Zhang Y
通讯作者：
Zhang Y
影响因子：
4.4
作者：
Cao S;Han J;Wu J;Li Q;Liu S;Zhang W;Pei Y;Ruan X;Liu Z;Wang X;Lim B;Li N
通讯作者：
Li N
DOI：
10.1073/pnas.1321569111
发表时间：
2014-03-18
影响因子：
11.1
作者：
Graf, Alexander;Krebs, Stefan;Wolf, Eckhard
通讯作者：
Wolf, Eckhard
影响因子：
64.5
作者：
Matoba S;Liu Y;Lu F;Iwabuchi KA;Shen L;Inoue A;Zhang Y
通讯作者：
Zhang Y