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Status |
Public on Aug 14, 2018 |
Title |
Inhibition of aberrant DNA re-methylation improves development of cloned embryos (WGBS-Seq) |
Organism |
Mus musculus |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
Somatic cell nuclear transfer (SCNT) enables the genome of a differentiated somatic cell to be reprogrammed to totipotency. However, this process is extremely inefficient, and the underlying mechanism of the epigenetic rearrangements following SCNT remains largely unknown. Here, we generated a genome-wide DNA methylome of mouse SCNT preimplantation embryos. Surprisingly, we identified widespread re-methylated regions (rDMRs) in 2- to 4-cell stage cloned embryos, which caused mis-expression of genes and retrotransposons important for zygotic genome activation and embryo development. Knocking-down DNA methyltransferases can specifically rescue the re-methylation defects of SCNT embryos and evidently improve the poor developmental capacity of cloned embryos. In addition, inactivation of DNA methyltransferases combined with overexpression of histone demethylases led to a more significant reduction in DNA methylation as well as exhibited a synergistic enhancement effect on the full-term development of nuclear transfer embryos. Our study therefore reveals that aberrant re-methylation functions as an unavoidable barrier for SCNT embryo development, and that the removal of multiple epigenetic barriers would be a promising approach to achieve the highest cloning efficiency.
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Overall design |
For SCNT embryos, 1-2 replicates were performed for each stage.
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Contributor(s) |
Wang C, Gao R, Xiu W, Liu W, Gao Y, Kou X, Zhao Y, Bai D, Zhang Y, Gao S |
Citation missing |
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Submission date |
Jun 21, 2018 |
Last update date |
Mar 19, 2019 |
Contact name |
Shaorong Gao |
Organization name |
Tongji University
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Department |
School of life science and technology
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Lab |
Gaolab
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Street address |
1239 Siping Road, Yangpu District
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City |
Shanghai |
State/province |
Shanghai |
ZIP/Postal code |
200092 |
Country |
China |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (23)
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This SubSeries is part of SuperSeries: |
GSE108711 |
Inhibition of aberrant DNA re-methylation improves development of cloned embryos |
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Relations |
BioProject |
PRJNA477280 |
SRA |
SRP151020 |