Inhibition of Aberrant DNA Re-methylation Improves Post-implantation Development of Somatic Cell Nuclear Transfer

Rui Gao1, Chenfei Wang1, Yawei Gao1

  • 1Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

Cell Stem Cell
|August 28, 2018
PubMed

Insights

Cloning via somatic cell nuclear transfer (SCNT) is inefficient due to epigenetic errors. Inhibiting DNA methyltransferases (DNMTs) and histone demethylases improves cloned embryo development by correcting DNA methylation issues.

Area of Science:

  • Epigenetics
  • Developmental Biology
  • Genomics

Background:

  • Somatic cell nuclear transfer (SCNT) is a technique for cloning cells, but its efficiency is limited by epigenetic abnormalities in cloned embryos.
  • Epigenetic reprogramming errors, particularly in DNA methylation, hinder the full-term development of SCNT embryos.

Purpose of the Study:

  • To investigate genome-wide DNA methylation patterns in mouse SCNT embryos.
  • To identify epigenetic barriers limiting SCNT efficiency.
  • To explore therapeutic strategies for improving SCNT outcomes.

Main Methods:

  • Generation of genome-wide DNA methylation maps from pre-implantation mouse SCNT embryos.
  • Analysis of gene and retrotransposon expression in SCNT embryos.
  • Pharmacological inhibition of DNA methyltransferases (DNMTs).
  • Overexpression of histone demethylases.

Main Results:

  • Identified widespread aberrant DNA re-methylation in SCNT embryos, affecting genes crucial for zygotic genome activation.
  • DNMT inhibition alone partially rescued methylation defects and improved embryo development.
  • Combined DNMT inhibition and histone demethylase overexpression synergistically reduced aberrant DNA methylation and significantly enhanced full-term SCNT embryo development.

Conclusions:

  • Excessive DNA re-methylation is a major impediment to efficient SCNT.
  • Targeting multiple epigenetic barriers, such as aberrant DNA methylation, offers a promising strategy to increase cloning efficiency.

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