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TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos

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...

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Autores principales: Liu, Xin, Chen, Lu, Wang, Tao, Zhou, Jilong, Li, Zhekun, Bu, Guowei, Zhang, Jingjing, Yin, Shuyuan, Wu, Danya, Dou, Chengli, Xu, Tian, He, Hainan, Zhu, Wei, Yu, Longtao, Liu, Zhiting, Zhang, Xia, Chen, Zhen-Xia, Miao, Yi-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581057/
https://www.ncbi.nlm.nih.gov/pubmed/34678203
http://dx.doi.org/10.1016/j.stemcr.2021.09.012
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author Liu, Xin
Chen, Lu
Wang, Tao
Zhou, Jilong
Li, Zhekun
Bu, Guowei
Zhang, Jingjing
Yin, Shuyuan
Wu, Danya
Dou, Chengli
Xu, Tian
He, Hainan
Zhu, Wei
Yu, Longtao
Liu, Zhiting
Zhang, Xia
Chen, Zhen-Xia
Miao, Yi-Liang
author_facet Liu, Xin
Chen, Lu
Wang, Tao
Zhou, Jilong
Li, Zhekun
Bu, Guowei
Zhang, Jingjing
Yin, Shuyuan
Wu, Danya
Dou, Chengli
Xu, Tian
He, Hainan
Zhu, Wei
Yu, Longtao
Liu, Zhiting
Zhang, Xia
Chen, Zhen-Xia
Miao, Yi-Liang
author_sort Liu, Xin
collection PubMed
description 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.
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spelling pubmed-85810572021-11-18 TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos Liu, Xin Chen, Lu Wang, Tao Zhou, Jilong Li, Zhekun Bu, Guowei Zhang, Jingjing Yin, Shuyuan Wu, Danya Dou, Chengli Xu, Tian He, Hainan Zhu, Wei Yu, Longtao Liu, Zhiting Zhang, Xia Chen, Zhen-Xia Miao, Yi-Liang Stem Cell Reports Article 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. Elsevier 2021-10-21 /pmc/articles/PMC8581057/ /pubmed/34678203 http://dx.doi.org/10.1016/j.stemcr.2021.09.012 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Xin
Chen, Lu
Wang, Tao
Zhou, Jilong
Li, Zhekun
Bu, Guowei
Zhang, Jingjing
Yin, Shuyuan
Wu, Danya
Dou, Chengli
Xu, Tian
He, Hainan
Zhu, Wei
Yu, Longtao
Liu, Zhiting
Zhang, Xia
Chen, Zhen-Xia
Miao, Yi-Liang
TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos
title TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos
title_full TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos
title_fullStr TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos
title_full_unstemmed TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos
title_short TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos
title_sort tdg is a pig-specific epigenetic regulator with insensitivity to h3k9 and h3k27 demethylation in nuclear transfer embryos
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581057/
https://www.ncbi.nlm.nih.gov/pubmed/34678203
http://dx.doi.org/10.1016/j.stemcr.2021.09.012
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