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Cell Stem Cell January 1, 2017; 21 (1): 135-143.e6.

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

Hörmanseder E , Simeone A , Allen GE , Bradshaw CR , Figlmüller M , Gurdon J , Jullien J .

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.

PubMed ID: 28366589
PMC ID: PMC5505866
Article link: Cell Stem Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: a2m darmin gata6 kdm5b sox17b.1 sox17b.2

GEO Series: GSE92366: NCBI

Article Images: [+] show captions
References [+] :
Alexa, Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. 2006, Pubmed