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H3K4 Methylation-Dependent Memory of Somatic Cell Identity Inhibits Reprogramming and Development of Nuclear Transfer

Eva Hörmanseder1, Angela Simeone1, George E Allen1

  • 1Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.

Cell Stem Cell
|April 4, 2017
PubMed

Insights

Reducing H3K4 methylation improves nuclear reprogramming and cloned animal development. This epigenetic modification acts as a barrier, and lowering it enhances the efficiency of nuclear transfer (NT) embryo development.

Area of Science:

  • Epigenetics
  • Developmental Biology
  • Reproductive Science

Background:

  • Vertebrate eggs can reprogram somatic cell nuclei for cloning.
  • Nuclear reprogramming is often inefficient, leading to compromised embryo development.
  • Inappropriate gene expression from donor nuclei is a key issue.

Purpose of the Study:

  • To identify epigenetic factors limiting nuclear reprogramming and nuclear transfer (NT) efficiency.
  • To investigate the role of H3K4 methylation in epigenetic memory and gene expression in NT embryos.
  • To determine if reducing H3K4 methylation can improve NT embryo development.

Main Methods:

  • Analysis of gene expression in nuclear transfer (NT) embryos.
  • Assessment of H3K4 methylation levels in donor cells and NT embryos.
  • Experimental manipulation of H3K4 methylation levels in donor cells.
  • Evaluation of NT embryo development after H3K4 methylation reduction.

Main Results:

  • High H3K4 methylation in donor cells creates an epigenetic barrier to reprogramming.
  • Donor-cell-specific genes were inappropriately expressed in NT embryos due to H3K4 methylation.
  • Reducing H3K4 methylation improved transcriptional reprogramming in NT embryos.
  • Lowering H3K4 methylation enhanced the developmental capacity of NT embryos.

Conclusions:

  • H3K4 methylation is a significant epigenetic roadblock to efficient nuclear reprogramming.
  • Targeting H3K4 methylation can overcome epigenetic memory and improve cloning outcomes.
  • Strategies to reduce H3K4 methylation offer a promising approach to enhance nuclear transfer efficiency.
Keywords:
H3K4me3Kdm5bcell-fate stabilityendodermepigenetic memorynuclear transferreprogramming

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