Scientists at the Centre for Genomic Regulation (CRG) in collaboration with the Josep Carreras Leukaemia Research Institute and The Institute for Health Science Research Germans Trias i Pujol have discovered that impaired DNA replication can also cause large epigenetic changes. Their Caenorhabditis elegans study, published in Science Advances, suggests that these epigenetic alterations can be inherited for up-to five generations.
For the correct function of cells and ultimately the health of the organism, it is important to keep certain genes active and others silenced," explained Tanya Vavouri, a co-author of the study. Inside cells, there are DNA-protein complexes called heterochromatin that prevent genes from becoming activated when they should not be. Initially, we noticed that a gene artificially inserted into the worm genome and normally silenced by heterochromatin was activated in animals that carried mutations in proteins involved in the copying of DNA. We found that this was caused by loss of heterochromatin and that other genes also silenced by heterochromatin were activated too. Unexpectedly, the gene was inappropriately activated for five generations in animals that did not carry the mutation in DNA replication but had ancestors that did."
The study showed that impaired DNA replication can cause genetic alterations and genome-wide epigenetic changes that are inheritable between generations. The scientists hope to understand more and to what extent can epigenetic states be transmitted between generations.
Image: Adult C. elegans worms can be seen with embryos inside them. Image courtesy of: Adam Klosin, CRG