A multicolour polymer model for the prediction of 3D structure and transcription in human chromatin

Within each human cell three types of RNA polymerases and a panoply of different transcription factors bind chromatin to simultaneously determine 3D chromosome structure and cells transcriptional program. In some cases different types of proteins segregate to form specialised transcription factories, while in others they mix and gather together, binding the same chromatin regions. We introduce a polymer model which accounts for multiple types -- or ``colours'' -- of DNA-binding proteins. Molecular dynamics simulations shows a good agreement with experimental data, and the appearance of stable segregated/specialised and mixed clusters suggesting a transition between the two types based on their size.

The inclusion of different types of proteins also introduces non-trivial positive and negative spatiotemporal correlations between different transcription units, giving rise to non-trivial effects due to local mutations or transcription units and factor density changes. Our results reconcile experimental observations on specialised and mixed clusters of DNA-binding proteins, and suggest that transcription factor identity is a key feature to include in polymer models for chromosome structure and transcription.