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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
Summary
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.