Changing cell fate by nuclear reprogramming.
The differentiated state of somatic cells is remarkably stable, but nuclear transfer can efficiently override the stability of cell differentiation by nuclear reprogramming. Genes that were silent in the differentiated state are activated, whereas genes specific for the differentiated state are switched off during the reprogramming process. The epigenetic changes that occur after nuclear transfer to Xenopus oocytes involve chromatin remodelling and DNA demethylation. In particular, we have reported that reactivation of the mouse stem cell specific gene oct-4 depends on demethylation of CpG:s in the proximal oct-4 promoter. Here we discuss molecular mechanisms of nuclear reprogramming, with special emphasis on DNA demethylation.
Simonsson
Stina
S
Department of Medical Biochemistry, Goteborg, Sweden. stina.simonsson@medkem.gu.se
Gurdon
J B
JB
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D019976:Cloning, Organism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D015530:Nuclear Matrix; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology; D014158:Transcription, Genetic; D014981:Xenopus
D002843:Chromatin; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse