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Inhibition of aberrant DNA re-methylation improves development of cloned embryos

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE108711 | GEO | 2018/08/14

REPOSITORIES: GEO

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Inhibition of aberrant DNA re-methylation improves development of cloned embryos (WGBS-Seq)

Project description: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.

2018-08-14 | GSE116103 | GEO

Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RRBS-Seq)

2018-08-14 | GSE108708 | GEO

Inhibition of aberrant DNA re-methylation improves development of cloned embryos

Project description:Inhibition of aberrant DNA re-methylation improves development of cloned embryos

| PRJNA428351 | ENA

Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RNA-Seq data set 2)

2018-08-14 | GSE116104 | GEO

Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RNA-Seq data set 1)

2018-08-14 | GSE108710 | GEO

Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RRBS-Seq)

Project description:Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RRBS-Seq)

| PRJNA428419 | ENA

Inhibition of aberrant DNA re-methylation improves development of cloned embryos (WGBS-Seq)

Project description:Inhibition of aberrant DNA re-methylation improves development of cloned embryos (WGBS-Seq)

| PRJNA477280 | ENA

Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RNA-Seq data set 1)

Project description:Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RNA-Seq data set 1)

| PRJNA428420 | ENA

Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RNA-Seq data set 2)

Project description:Inhibition of aberrant DNA re-methylation improves development of cloned embryos (RNA-Seq data set 2)

| PRJNA477282 | ENA

Osteoponin promoter controlled by DNA methylation: aberrant methylation in cloned porcine genome.

Project description:Cloned animals usually exhibited many defects in physical characteristics or aberrant epigenetic reprogramming, especially in some important organ development. Osteoponin (OPN) is an extracellular-matrix protein involved in heart and bone development and diseases. In this study, we investigated the correlation between OPN mRNA and its promoter methylation changes by the 5-aza-dc treatment in fibroblast cell and promoter assay. Aberrant methylation of porcine OPN was frequently found in different tissues of somatic nuclear transferred cloning pigs, and bisulfite sequence data suggested that the OPN promoter region -2615 to -2239 nucleotides (nt) may be a crucial regulation DNA element. In pig ear fibroblast cell culture study, the demethylation of OPN promoter was found in dose-dependent response of 5-aza-dc treatment and followed the OPN mRNA reexpression. In cloned pig study, discrepant expression pattern was identified in several cloned pig tissues, especially in brain, heart, and ear. Promoter assay data revealed that four methylated CpG sites presenting in the -2615 to -2239 nt region cause significant downregulation of OPN promoter activity. These data suggested that methylation in the OPN promoter plays a crucial role in the regulation of OPN expression that we found in cloned pigs genome.

| S-EPMC4102072 | biostudies-literature

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