EMBRYONIC GERM-CELLS INDUCE EPIGENETIC REPROGRAMMING OF SOMATIC NUCLEUS IN HYBRID-CELLS

Genomic reprogramming of primordial germ cells (PGCs), which includes genome-wide demethylation, prevents aberrant epigenetic modifications from being transmitted to subsequent generations, This process also en sures that homologous chromosomes first acquire an identical epigeneti c status before an appropriate switch in the imprintable loci in the f emale and male germ lines. Embryonic germ (EG) cells have a similar ep igenotype to PGCs from which they are derived, We used EG cells to inv estigate the mechanism of epigenetic modifications in the germ line by analysing the effects on a somatic nucleus in the EG-thymic lymphocyt e hybrid cells. There were striking changes in methylation of the soma tic nucleus, resulting in demethylation of several imprinted and non-i mprinted genes, These epigenetic modifications were heritable and affe cted gene expression as judged by re-activation of the silent maternal allele of Peg1/Mest imprinted gene in the somatic nucleus. This remar kable change in the epigenotype of the somatic nucleus is consistent w ith the observed pluripotency of the EG-somatic hybrid cells as they d ifferentiated into a variety of tissues in chimeric embryos. The epige netic modifications observed in EG-somatic cell hybrids in vitro are c omparable to the reprogramming events that occur during germ cell deve lopment.