Active and Passive Demethylation of Male and Female Pronuclear DNA in the Mammalian Zygote

Fan Guo, Xianlong Li, Dan Liang, Tong Li, Ping Zhu, Hongshan Guo, Xinglong Wu, Lu Wen, Tian-Peng Gu, Boqiang Hu, Colum Walsh, Jinsong Li, Fuchou Tang, Guo-Liang Xu

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed during early embryogenesis to establish full developmental potential. Previous studies have suggested that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes subsequent passive demethylation via DNA replication during cleavage. Active demethylation is known to depend on 5mC oxidation by Tet dioxygenases and excision of oxidized bases by thymine DNA glycosylase (TDG). Here we show that both maternal and paternal genomes undergo widespread active and passive demethylation in zygotes before the first mitotic division. Passive demethylation was blocked by the replication inhibitor aphidicolin, and active demethylation was abrogated by deletion of Tet3 in both pronuclei. At actively demethylated loci, 5mCs were processed to unmodified cytosines. Surprisingly, the demethylation process was unaffected by the deletion of TDG from the zygote, suggesting the existence of other demethylation mechanisms downstream of Tet3-mediated oxidation.
LanguageEnglish
Pages447-458
Number of pages11
JournalCell Stem Cell
Volume15
Issue number4
DOIs
Publication statusPublished - 11 Sep 2014

Fingerprint

Thymine DNA Glycosylase
Zygote
5-Methylcytosine
Genome
DNA
Mothers
Aphidicolin
Dioxygenases
Cytosine
DNA Replication
Germ Cells
Oocytes
Embryonic Development
Spermatozoa

Keywords

  • Active demethylation
  • Passive demethylation
  • Zygote
  • 5hmC
  • Pronuclear DNA
  • TETs

Cite this

Guo, Fan ; Li, Xianlong ; Liang, Dan ; Li, Tong ; Zhu, Ping ; Guo, Hongshan ; Wu, Xinglong ; Wen, Lu ; Gu, Tian-Peng ; Hu, Boqiang ; Walsh, Colum ; Li, Jinsong ; Tang, Fuchou ; Xu, Guo-Liang. / Active and Passive Demethylation of Male and Female Pronuclear DNA in the Mammalian Zygote. In: Cell Stem Cell. 2014 ; Vol. 15, No. 4. pp. 447-458.
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Guo, F, Li, X, Liang, D, Li, T, Zhu, P, Guo, H, Wu, X, Wen, L, Gu, T-P, Hu, B, Walsh, C, Li, J, Tang, F & Xu, G-L 2014, 'Active and Passive Demethylation of Male and Female Pronuclear DNA in the Mammalian Zygote', Cell Stem Cell, vol. 15, no. 4, pp. 447-458. https://doi.org/10.1016/j.stem.2014.08.003

Active and Passive Demethylation of Male and Female Pronuclear DNA in the Mammalian Zygote. / Guo, Fan; Li, Xianlong; Liang, Dan; Li, Tong; Zhu, Ping; Guo, Hongshan; Wu, Xinglong; Wen, Lu; Gu, Tian-Peng; Hu, Boqiang; Walsh, Colum; Li, Jinsong; Tang, Fuchou; Xu, Guo-Liang.

In: Cell Stem Cell, Vol. 15, No. 4, 11.09.2014, p. 447-458.

Research output: Contribution to journalArticle

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AU - Guo, Fan

AU - Li, Xianlong

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AU - Zhu, Ping

AU - Guo, Hongshan

AU - Wu, Xinglong

AU - Wen, Lu

AU - Gu, Tian-Peng

AU - Hu, Boqiang

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AU - Li, Jinsong

AU - Tang, Fuchou

AU - Xu, Guo-Liang

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N2 - The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed during early embryogenesis to establish full developmental potential. Previous studies have suggested that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes subsequent passive demethylation via DNA replication during cleavage. Active demethylation is known to depend on 5mC oxidation by Tet dioxygenases and excision of oxidized bases by thymine DNA glycosylase (TDG). Here we show that both maternal and paternal genomes undergo widespread active and passive demethylation in zygotes before the first mitotic division. Passive demethylation was blocked by the replication inhibitor aphidicolin, and active demethylation was abrogated by deletion of Tet3 in both pronuclei. At actively demethylated loci, 5mCs were processed to unmodified cytosines. Surprisingly, the demethylation process was unaffected by the deletion of TDG from the zygote, suggesting the existence of other demethylation mechanisms downstream of Tet3-mediated oxidation.

AB - The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed during early embryogenesis to establish full developmental potential. Previous studies have suggested that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes subsequent passive demethylation via DNA replication during cleavage. Active demethylation is known to depend on 5mC oxidation by Tet dioxygenases and excision of oxidized bases by thymine DNA glycosylase (TDG). Here we show that both maternal and paternal genomes undergo widespread active and passive demethylation in zygotes before the first mitotic division. Passive demethylation was blocked by the replication inhibitor aphidicolin, and active demethylation was abrogated by deletion of Tet3 in both pronuclei. At actively demethylated loci, 5mCs were processed to unmodified cytosines. Surprisingly, the demethylation process was unaffected by the deletion of TDG from the zygote, suggesting the existence of other demethylation mechanisms downstream of Tet3-mediated oxidation.

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KW - Passive demethylation

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KW - 5hmC

KW - Pronuclear DNA

KW - TETs

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