Cell Cycle Volume 4 Issue 4 Authors: Stina Simonsson, J. B. Gurdon
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.
Cell Cycle Volume 7 Issue 9 Authors: Ray K. Ng, John B. Gurdon
Epigenetic modifications influence gene expression pattern and provide a unique signature of a cell differentiation status. Without external stimuli or signalling events, this cell identity remains stable and unlikely to change over many cell divisions. The epigenetic signature of a particular cell fate therefore needs to be replicated faithfully in daughter cells; otherwise a cell lineage cannot be maintained. However, the mechanism of transmission of cellular memory from mother to daughter cells remains unclear. It has been suggested that the inheritance of an active or silent gene state involves different kinds of epigenetic mechanisms, e.g. DNA methylation, histone modifications, replacement of histone variants, Polycomb group (PcG) and Trithorax group (TrxG) proteins. Emerging evidence supports the role of histone variant H3.3 in maintaining an active gene status and in remodelling nucleosomal composition. Here we discuss some recent findings on the propagation of epigenetic memory and propose a model for the inheritance of an active gene state through the interaction of H3.3 with other epigenetic components.
Cell Cycle Volume 4 Issue 6 Authors: Ray K. Ng, J. B. Gurdon
Different cell types have characteristic patterns of gene expression. Once a cell has..differentiated, its daughter cells nearly always differentiate in the same way. The..maintenance of cell lineage involves either instructions from a cell’s surroundings or..the inheritance of memory from a parent cell. In normal development, the..differentiation state of a cell is remarkably stable and irreversible. However the..transplantation of a somatic cell nucleus to an enucleated egg often leads to a..complete reprogramming of gene expression. We summarize here the results of some..Amphibian nuclear transfer experiments that reveal a memory of gene expression...This and some other experiments exemplify epigenetic memory that persists through..many cell divisions. In the case of nuclear transfer experiments, the actively..transcribed state of a gene can be propagated through many cell divisions in the..absence of the stimulus that first induced the activity of this gene. We discuss the..possible basis of these two examples of persistent epigenetic memory, namely..changes at DNA methylation, and histone modifications.