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Within each human cell, different kinds of RNA polymerases and a panoply oftranscription factors bind chromatin to simultaneously determine 3D chromosomestructure and transcriptional programme. Experiments show that, in some cases,different proteins segregate to form specialised transcription factories; inothers they mix together, binding promiscuously the same chromatin stretch.Here, we use Brownian dynamics simulations to study a polymer model forchromosomes accounting for multiple types ('colours') of chromatin-bindingproteins. Our multi-colour model shows the spontaneous emergence of bothsegregated and mixed clusters of chromatin-bound proteins, depending mainly ontheir size, thereby reconciling the previous experimental observations.Additionally, remarkable small-world networks emerge; in these, positive andnegative correlations in activities of transcription units provide simpleexplanations of why adjacent units in large domains are co-transcribed sooften, and how one eQTL (expression quantitative trait locus) can up-regulatesome genes and down-regulate others. We also explain how local genome editsinduce distant omnigenic and pangenomic effects, and develop ways to predictactivities of all transcription units on human chromosomes. All results pointto 1D location being a key determinant of transcription, consistently with theconservation of synteny seen between rapidly-evolving enhancers and their morestable target genes.

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