Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development
Ten-eleven translocation (Tet) dioxygenases can induce DNA demethylation by catalyzing 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), and play important roles during mammalian development. In mouse, Tet1 and Tet2 are not expressed in pronucleus-staged embryos and are not involved in the gen...
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| author | Qi Qi Qianqian Wang Kailing Liu Jiangyue Bian Zhixuan Yu Jian Hou |
| author_facet | Qi Qi Qianqian Wang Kailing Liu Jiangyue Bian Zhixuan Yu Jian Hou |
| author_sort | Qi Qi |
| collection | DOAJ |
| description | Ten-eleven translocation (Tet) dioxygenases can induce DNA demethylation by catalyzing 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), and play important roles during mammalian development. In mouse, Tet1 and Tet2 are not expressed in pronucleus-staged embryos and are not involved in the genomic demethylation of early zygotes. Here, we investigated the influence of Tet1 and Tet2 on methylation of parental genomes by ectopically expressing Tet1 and Tet2 in zygotes. Immunofluorescence staining showed a marked 5hmC increase in the maternal pronucleus after injection of Tet1 or Tet2 mRNA into zygotes. Whole-genome bisulfite sequencing further revealed that Tet2 greatly enhanced the global demethylation of both parental genomes, while Tet1 only promoted the paternal demethylation. Tet1 and Tet2 overexpression altered the DNA methylation across genomes, including various genic elements and germline-specific differently methylated regions. Tet2 exhibited overall stronger demethylation activity than Tet1. Either Tet1 or Tet2 overexpression impaired preimplantation embryonic development. These results demonstrated that early expression of Tet1 and Tet2 could substantially alter the zygotic methylation landscape and damage embryonic development. These findings provide new insights into understanding the function of Tet dioxygenases and the mechanism of DNA methylation in relation to embryogenesis. |
| first_indexed | 2024-03-09T12:32:06Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:32:06Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-c27ecd1614e24261ba25cceb52114f652023-11-30T22:28:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315849510.3390/ijms23158495Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic DevelopmentQi Qi0Qianqian Wang1Kailing Liu2Jiangyue Bian3Zhixuan Yu4Jian Hou5State Key Laboratory of Agrobiotechnology and College of Biological Science, China Agricultural University, Beijing 100193, ChinaState Key Laboratory of Agrobiotechnology and College of Biological Science, China Agricultural University, Beijing 100193, ChinaState Key Laboratory of Agrobiotechnology and College of Biological Science, China Agricultural University, Beijing 100193, ChinaState Key Laboratory of Agrobiotechnology and College of Biological Science, China Agricultural University, Beijing 100193, ChinaState Key Laboratory of Agrobiotechnology and College of Biological Science, China Agricultural University, Beijing 100193, ChinaState Key Laboratory of Agrobiotechnology and College of Biological Science, China Agricultural University, Beijing 100193, ChinaTen-eleven translocation (Tet) dioxygenases can induce DNA demethylation by catalyzing 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), and play important roles during mammalian development. In mouse, Tet1 and Tet2 are not expressed in pronucleus-staged embryos and are not involved in the genomic demethylation of early zygotes. Here, we investigated the influence of Tet1 and Tet2 on methylation of parental genomes by ectopically expressing Tet1 and Tet2 in zygotes. Immunofluorescence staining showed a marked 5hmC increase in the maternal pronucleus after injection of Tet1 or Tet2 mRNA into zygotes. Whole-genome bisulfite sequencing further revealed that Tet2 greatly enhanced the global demethylation of both parental genomes, while Tet1 only promoted the paternal demethylation. Tet1 and Tet2 overexpression altered the DNA methylation across genomes, including various genic elements and germline-specific differently methylated regions. Tet2 exhibited overall stronger demethylation activity than Tet1. Either Tet1 or Tet2 overexpression impaired preimplantation embryonic development. These results demonstrated that early expression of Tet1 and Tet2 could substantially alter the zygotic methylation landscape and damage embryonic development. These findings provide new insights into understanding the function of Tet dioxygenases and the mechanism of DNA methylation in relation to embryogenesis.https://www.mdpi.com/1422-0067/23/15/8495DNA methylationmicezygotesTet1Tet2embryonic development |
| spellingShingle | Qi Qi Qianqian Wang Kailing Liu Jiangyue Bian Zhixuan Yu Jian Hou Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development International Journal of Molecular Sciences DNA methylation mice zygotes Tet1 Tet2 embryonic development |
| title | Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development |
| title_full | Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development |
| title_fullStr | Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development |
| title_full_unstemmed | Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development |
| title_short | Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development |
| title_sort | early expression of tet1 and tet2 in mouse zygotes altered dna methylation status and affected embryonic development |
| topic | DNA methylation mice zygotes Tet1 Tet2 embryonic development |
| url | https://www.mdpi.com/1422-0067/23/15/8495 |
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