Final Report Summary - EPIRNAS (Small RNA Mediated Epigenetics in Vertebrates)
In addition, we identified a process in which small RNA molecules are modified during their lives in the cell. This process, named non-templated uridylation, signals that the modified small RNA needs to be degraded, and absence of this mechanism leads to inappropriate amounts of small RNAs that in turn lead to defects of how the genome is used.
In parallel, we have been looking at how a chemical modification of the DNA, named DNA methylation, changes during differentiation of a stem cell. DNA methylation is believed to be a signal that stably silences DNA, and the differentiation of a stem cell can be expected to be accompanied by many changes in DNA methylation, because many genes are turned on and off. In fact, DNA methylation is often described as ‘locking’ the silencing of the expression of genes. Unexpectedly, when we analyzed the DNA methylation pattern of stem cells from the small intestine of mice and compared that to the DNA methylation pattern of their differentiated descendant, only minor changes were observed. The changes that we did see were mostly indicative of DNA methylation being influenced by proteins binding to the DNA and not of DNA methylation patterns driving the differentiation process. This picture differs drastically with the pictures obtained from stem cells differentiating in vitro in cell cultures, and might be related to the fact that the differentiated daughters of intestinal stem cells only live shortly. Nevertheless, this work showed that changes in DNA methylation most likely do not drive differentiation of intestinal stem cells in mice.