Scientists at EPFL and UNIL have used a new algorithmic approach on cancer cells to gain knowledge and how changes in histone markers (H3K27ac) and induce repositioning of chromatin regions in the cell nucleus. The scientists have also described how modifications to local contacts between regulatory elements known as enhancers and promoters influence oncogene expression. The research is attempting to gain a new understanding of cancer and potential methods to fight it.
Cancer is an extremely complex disease which is in part what makes research into cancer so difficult. To gain an understanding into cancer, researchers focus attention on the genome. If they can understand what happens at the level of DNA, scientists hope it would be possible to treat and prevent cancers altogether in the future. Researchers on this project have made a breakthrough discovery concerning a critical genetic aberration that happens in cancer.
The team used a novel algorithm-based method to study how cancer cells reorganize the 3D structure of DNA to ramp up the activity of cancer-promoting genes known as oncogenes. Scientists focused on four chromosomes where DNA is packed inside the cell and how the chromosomes are organized inside the small confines of the cellular nucleus. In normal DNA, each cell carries 23 chromosomes and two copies for each chromosome. However, the structure and organization of chromosomes change in cancer cells.
Scientists say that a piece of a copy of chromosome 8 can be attached to a copy of chromosome 14 in a cancer cell. Chromosomes can also take on a more relaxed or compact structure depending on chemical modifications called epigenetic marks. Scientists on this project investigated how changes in specific epigenetic marks modify chromosome structures and the expression of genes promoting tumor growth known as oncogenes.
The genetic algorithm approach used by the team is called Calder and tracked how genomic regions are positioned with respect to each other inside the nucleus. The team used the approach to compare the spatial organization of the genome in more than 100 samples. Calder tracked regions of chromatin that “moved” from one area of the nucleus to another due to changing epigenetic marks. Teams discovered that in lymphoma cells, specific epigenetic changes cause chromatin regions to be repositioned into different areas of the nucleus leading to new local interactions that over-activate the expression of oncogenes.