Scientists gain new insights into genetic switches
The hormone oestrogen can cause genes in breast cancer cells to be switched on and off more rapidly than had been previously assumed, European researchers have found. The scientists hope their findings will shed new light on the molecular bases of cancer and development, both of which involve these DNA switches. The work, which was partly funded by the EU, is published in the latest edition of the journal Nature. Only a small number of our genes are active in any given tissue. For example, a gene which is active in a nerve cell may not be active in a liver cell. The mechanisms responsible for controlling which genes are switched on and when are the subject of a lot of research. One of the most important mechanisms is called DNA methylation, in which a chemical residue called a methyl group is attached to sections of the DNA. The methyl group shuts down gene activity by effectively preventing the cell machinery from attaching itself to the gene and triggering the production of the relevant protein. Until now, scientists had thought that methylation was a long term process because the methylation marks appear to be stable and are even passed on intact when the cell divides. However, this latest piece of research shows that in breast cancer cells, oestrogen and certain drugs can cause rapid changes in methylation. When oestrogen is withdrawn from the cell culture, or if the cells are treated with the anti-cancer drug doxorubicin, the methyl groups are removed from the regulatory regions of certain genes within tens of minutes. With the methyl groups removed, the genes become active, before remethylation shuts them down again. This process also turns out to be cyclical, repeating itself every 1.5 hours. 'We observed that, unlike assumed for a long time, methylation can act on a very short timescale,' said Sara Kangaspeska of the European Molecular Biology Laboratory (EMBL). 'The results challenge our understanding of epigenetics as a means to regulate gene expression permanently.' 'The new insight paves the way for research on methods to interfere with the methylation process,' commented Frank Gannon of Science Foundation Ireland. 'As this is central to the expression of genes which are important in cancer and development it should prove to be a very fruitful area of research.' 'In particular breast cancer is affected by oestrogen signalling and changes in epigenetic control,' added George Reid, also of the EMBL. 'Our next step will be to find small molecules that target the cyclical methylation process to elucidate their precise role.' The work was supported by the EU-funded CRESCENDO ('Consortium for research into nuclear receptors in development and ageing') project, which is financed through the 'Life sciences, genomics and biotechnology for health' thematic area of the Sixth Framework Programme (FP6).