Impact Factor:7.765

DOI number:10.1016/j.stemcr.2021.09.012

Journal:Stem Cell Reports (C刊)

Abstract: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.

Co-author:Zhou JL,Li ZK,Bu GW,Zhang JJ,Yin SY,Wu DY,Dou CL,Xu T,He HN,Zhu W,Yu LT,Liu ZT,Zhang X

First Author:Liu X#,Chen L#,Wang T#

Indexed by:Journal paper

Correspondence Author:Miao YL*,Chen ZX*

Volume:16

Issue:11

Page Number:2674-2689

Translation or Not:no

Date of Publication:2021-10-21

Included Journals:SCI

Links to published journals:https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00489-6