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Transcriptional activity has been shown to relate to the organization ofchromosomes in the eukaryotic nucleus and in the bacterial nucleoid. Inparticular, highly transcribed genes, RNA polymerases and transcription factorsgather into discrete spatial foci called transcription factories. However, themechanisms underlying the formation of these foci and the resulting topologicalorder of the chromosome remain to be elucidated. Here we consider athermodynamic framework based on a worm-like chain model of chromosomes wheresparse designated sites along the DNA are able to interact whenever they arespatially close-by. This is motivated by recurrent evidence that there existsphysical interactions between genes that operate together. Three importantresults come out of this simple framework. First, the resulting formation oftranscription foci can be viewed as a micro-phase separation of the interactingsites from the rest of the DNA. In this respect, a thermodynamic analysissuggests transcription factors to be appropriate candidates for mediating thephysical interactions between genes. Next, numerical simulations of the polymerreveal a rich variety of phases that are associated with different topologicalorderings, each providing a way to increase the local concentrations of theinteracting sites. Finally, the numerical results show that bothone-dimensional clustering and periodic location of the binding sites along theDNA, which have been observed in several organisms, make the spatialco-localization of multiple families of genes particularly efficient.

Spatial and topological organization of DNA chains induced by gene co-localization