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30.03.17 Epigenetic memory of somatic cell identity inhibits reprogramming in nuclear transfer

last modified Jul 07, 2017 06:19 PM
The Gurdon lab show that genes retain a memory of their identity and active state that underlies resistance to reprogramming in nuclear transfer
30.03.17 Epigenetic memory of somatic cell identity inhibits reprogramming in nuclear transfer

Graphical abstract from the paper in Cell Stem Cell

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

Hörmanseder et al. (2017) Cell Stem Cell  vol 21, issue 1. doi: 10.1016/j.stem.2017.03.003 

 

Highlights

  • Nuclear transfer embryos retain the memory of a past state of active transcription (ON-memory)
  • ON-memory genes are enriched for H3K4 methylation in somatic donor nuclei
  • H3K4 demethylation improves transcriptional reprogramming
  • Removing H3K4 methylation enhances the development of nuclear transfer embryos

Summary from the paper

Vertebrate eggs can induce the nuclear reprogramming of somatic cells to enable production of cloned animals. Nuclear reprogramming is relatively
inefficient, and the development of the resultant embryos is frequently compromised, in part due to the inappropriate expression of genes previously active in the donor nucleus.

Here, we identify H3K4 methylation as a major epigenetic roadblock that limits transcriptional reprogramming and efficient
nuclear transfer (NT). Widespread expression of donor-cell-specific genes was observed in inappropriate cell types in NT embryos, limiting their developmental
capacity. The expression of these genes in reprogrammed embryos arises from epigenetic memories of a previously active transcriptional state in donor cells that is characterized by high H3K4 methylation. Reducing H3K4 methylation had little effect on gene expression in donor cells, but it substantially improved transcriptional reprogramming and development of NT embryos.

These results show that H3K4 methylation imposes a barrier to efficient nuclear reprogramming and suggest approaches for improving reprogramming strategies.

 

Read more about research in the Gurdon lab, and about another recent publication from the lab on this topic.

 

Summary and graphical abstract from the paper reproduced under Creative Commons (CC BY 4.0).

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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