影响因子：5.391

DOI码：10.1096/fj.201801887R

发表刊物：FASEB Journal (C刊)

摘要：Aberrant epigenetic reprogramming is a major factor of developmental failure of cloned embryos. Histone H3 lysine 27 trimethylation (H3K27me3), a histone mark for transcriptional repression, plays important roles in mammalian embryonic development and induced pluripotent stem cell (iPSC) generation. The global loss of H3K27me3 marks may facilitate iPSC generation in mice and humans. However, the H3K27me3 level and its role in bovine somatic cell nuclear transfer (SCNT) reprogramming remain poorly understood. Here, we show that SCNT embryos exhibit global H3K27me3 hypermethylation from the 2- to 8-cell stage and that its removal by ectopically expressed H3K27me3 lysine demethylase (KDM)6A greatly improves nuclear reprogramming efficiency. In contrast, H3K27me3 reduction by H3K27me3 methylase enhancer of zeste 2 polycomb repressive complex knockdown or donor cell treatment with the enhancer of zeste 2 polycomb repressive complex—selective inhibitor GSK343 suppressed blastocyst formation by SCNT embryos. KDM6A overexpression enhanced the transcription of genes involved in cell adhesion and cellular metabolism and X-linked genes. Furthermore, we identified methyl-CpG-binding domain protein 3-like 2, which was reactivated by KDM6A, as a factor that is required for effective reprogramming in bovines. These results show that H3K27me3 functions as an epigenetic barrier and that KDM6A overexpression improves SCNT efficiency by facilitating transcriptional reprogramming.

合写作者：Zhang JC,Su JM,An QL,Liu X,Zhang M,Wang YS,Liu J

第一作者：Zhou C#,Wang YZ#

论文类型：期刊论文

通讯作者：Zhang Y*

卷号：33

期号：3

页面范围：4638-4652

是否译文：否

发表时间：2019-01-23

收录刊物：SCI

发布期刊链接：https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201801887R