Gene transcription regulates the spatiotemporal genome organization through micro-phase separation mediated by RNA Polymerase-II
Enhancer-promoter interactions are widely recognized as crucial for gene expression. However, the impact of RNA Polymerase II (Pol II)-mediated activity on genome folding remains a subject of debate. In this study, we examine Micro-C data from mESCs and Drosophila embryos and reveal a significant correlation between the intra-gene contacts and Pol II occupancy within the gene region, independent of cohesin-dependent loop extrusion activity. To elucidate these findings, we develop a biophysical model that integrates a mathematical description of gene transcription with a polymer model of chromosome organization, incorporating effective Pol II-Pol II attractive interactions. Through systematic analysis of the model, we mechanistically investigate the spatio-temporal dynamics of genes and explore the influence of gene length, gene activity, and transcriptional bursting, yielding results consistent with experimental observations. Our work provides compelling evidence that transcriptional activity shapes the 4D genome through (micro)phase separation mediated by Pol II.