Coupling chromatin folding with histone modifications reveals dynamical asymmetry in the epigenetic landscape

Abstract

Genomic regions adopt heritable epigenetic states with unique histone modifications, resulting in bistable gene expression without changes to the underlying DNA sequence. The significance of chromatin conformational dynamics to epigenetic stability is not well understood. We introduce a kinetic model to simulate the dynamic fluctuation of histone modifications. The model explicitly incorporates the impact of chemical modifications on chromatin stability as well as the contribution of chromatin contacts to the cooperativity of chemical reactions. Leveraging the model’s computational efficiency, we study the disparate time scales of chromatin relaxation and epigenetic spread to account for the recent discovery of both liquid and gel-like properties of chromatin. Strikingly different results were obtained for the steady state and kinetic behavior of histone modification patterns in fast and slow chromatin structural relaxation regimes. Our study suggests that the timescale of chromatin conformational dynamics maybe an important axis that biology fine tunes to regulate epigenetic stability.