Seminar by Adrien Raymond Berard

Epigenetic memory achieved through chromatin-induced phase separation

Adrien Raymond Berard, Master's Student, Sorbonne University, Paris, France

Chromatin structure is a core determinant of gene expression and epigenetic inheritance. It relies on the post-translational modification of histones, the 3D folding of chromatin in the nucleus, and the capacity of chromatin components to engage in homotypic and heterotypic interactions. To understand how these elements cooperate, we employed molecular dynamics simulations integrating LAMMPS-based polymer modeling with enzymatic reactions occurring on nucleosomes (3-state model). A diffusible heterochromatic nucleosome reader, Swi6/HP1, was explicitly modeled whose binding to heterochromatic nucleosomes resulted in the targeted recruitment of histone deacetylases (HDACs).

The simulations revealed emerging properties that included the formation of heterochromatic domain condensates coated by Swi6/HP1. Domains were induced through 3D proximity effects, spatially separated domains competed for limiting components, and the simulations identified conditions for bistability and confined chromatin states. These behaviors reveal how synergies between chromatin modifiers and chromatin architecture lead to the emergence of epigenetically stable chromatin states.