CRG: Link between defects in DNA replication and loss of heterochromatin

CRG: Link between defects in DNA replication and loss of heterochromatin

News from CRG

Scientists at the CRG in collaboration with the Josep Carreras Leukaemia Research Institute (IJC) and the Institute for Health Science Research Germans Trias i Pujol (IGTP) have discovered that impaired DNA replication can cause large epigenetic changes. Their study, which was performed in worms (the model organism Caenorhabditis elegans), suggests that these genome-wide epigenetic alterations establish new gene expression states that may be inherited for up-to five generations. 

The researchers, led by ICREA research professor Ben Lehner, also identified the mechanism causing these epigenetic changes. “For the correct function of cells and ultimately the health of the organism, it is important to keep certain genes active and others silenced. 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,” explains Tanya Vavouri, coauthor of this study.

“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,” she adds.

More information:
CRG website

A. Klosin, K. Reis, C. Hidalgo-Carcedo, E. Casas, T. Vavouri, B. Lehner. “Impaired DNA replication derepresses chromatin and generates a transgenerational inherited epigenetic memory”. Science Advances. 3, e1701143 (2017). DOI: 10.1126/sciadv.1701143.

A. Klosin, E. Casas, C. Hidalgo-Carcedo, T. Vavouri, B. Lehner. "Transgenerational transmission of environmental information in C. elegans". Science. 356 (6335), 320-323 (2017). DOI: 10.1126/science.aah6412