A new publication: Theroretical model summarising 73 papers on Polycomb/Trithorax biochemistry finds bistability instead of bivalency as preferred system state.

June 20th, 2019.

Congratulations to Leonie Ringrose and Kim Sneppen.

Their paper Theoretical analysis of Polycomb-Trithorax systems predicts that poised chromatin is bistable and not bivalent was published in Nature Communications today!

Bistable properties of the PcG/TrxG regulatory system have long been proposed but until recently had not been investigated systematically. In this paper, we curated 73 publications on PcG/TrxG biochemistry and formalised the system as a dynamic stochastic mathematical model with 144 nucleosome states. Surprisingly, despite the large number of possible states, the model system is robustly bistable, preferring extreme active or silent, but not intermediate states. Importantly ,we show theoretically that bistability not only ensures epigenetic memory but is also as a central feature of poised, or ‘flexible’ chromatin. The difference in the model between stable and flexible modes is the frequency of switching between states (slow= stable, fast = flexible). Bivalent forms containig opposite histone modifications on the same nucleoseome exist in the model, but are transient intermediates and do not stably persist. This work has implications for understanding the molecular nature of pluripotency and the stability and reversibility of epigenetic states.

Theoretical model organises nucleosome states, readers, writers and erasers into a coherent framework. The system was simulated as a dynamic stochastic agent-based model.