H3K4 Methylation-Dependent Memory of Somatic Cell Identity Inhibits Reprogramming and Development of Nuclear Transfer Embryos
Hörmanseder et al. (2017) Cell Stem Cell doi: 10.1016/j.stem.2017.03.003 (Advance online publication)]
- 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.
Summary and graphical abstract from the paper reproduced under Creative Commons (CC BY 4.0).