Biophysical principles for chromosome organisation: biogenesis of nuclear bodies and 3D epigenetic dynamics

In the first part of the talk I will describe a biophysical model for the formation and dynamics of "nuclear bodies", DNA-protein complexes such as the nucleolus, Cajal, polycomb bodies, or transcription factories. The model is based on Brownian dynamics simulations of chromatin fibres and whole chromosomes interacting with bivalent of multivalent (architectural) chromatin-binding proteins (transcription factors). The model also provides potential solutions to some puzzles conserning the actions of enhancers, super-enhancers, and expression quantitative trait loci (eQTLs).

In the second part of this talk I will discuss a variation of this model where chromatin segments are characterised by a variable "epigenetic" state, modelling histone modifications such as acetylation and methylation, which are associated with local genomic transcriptional activity. We will see that 3D chromatin organisation and dynamic epigenetic landscape are intimately coupled, that this coupling paves the way to the establishment of epigenetic domains on chromosomes, and may provide a biophysical mechanism underpinning epigenetic memory.