Biophysical principles of chromosome organisation and transcriptional dynamics I will discuss our ongoing collaborative work combining polymer physics, computer simulations and experiments to understand the way in which human chromatin is organised in 3D space in living cells, and how this organisation in turn affects transcription, or gene expression (see https://3dgene.igc.ed.ac.uk). We will review evidence from computer simulations and polymer modelling which suggests multivalent chromatin-binding proteins generically cluster to form functional droplets of polymerases, transcription factors and genomic binding sites. By combining modelling and super-resolution microscopy, we further show these transcriptionally active clusters are associated with a self-organised interconnected network of microgels made of RNA, chromatin and RNA-binding proteins. I will then discuss how we have been using a similar combination of theory and experiments to propose a molecular mechanism underlying transcriptional noise, which plays a key role in developmental biology and disease, and a pathway through which torsional stress associated with DNA supercoiling can be harnessed to regulate gene expression. This article was published on 2025-10-29
