Dra. Daria Stepanova – Modelling the interplay between epigenetic regulation and chromatin conformation

The packaging of genetic information within cells relies on the efficient organisation of DNA. This packing begins with wrapping the DNA double helix around nucleosomes, forming the complex called chromatin. Epigenetic regulation, involving the dynamic interplay of various epigenetic marks that can be added and removed from the chromatin, significantly shapes the three-dimensional folding of the chromatin polymer and, consequently, regulates gene expression.

I will present our modelling study, which delves into epigenetic regulation in the context of a 3D-folded polymer. Our model incorporates modifications of lysine residues H3K4 and H3K27, with feedback loops originating from interactions between genomic loci in close proximity in three-dimensional space. Our modelling results showcase the model’s behaviour. Our findings also demonstrate the model’s ability to capture the formation of rugged epigenetic profiles, which flatten under conditions marked by increased double-strand breaks, characteristic of cancer and ageing.