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Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization.
Nat Commun, 15(1):5393.
Although our understanding of the involvement of heterochromatin architecturalfactors in shaping nuclear organization is improving, there is still ongoingdebate regarding the role of active genes in this process. In this study, weutilize publicly-available Micro-C data from mouse embryonic stem cells toinvestigate the relationship between gene transcription and 3D gene folding. Ouranalysis uncovers a nonmonotonic - globally positive - correlation betweenintragenic contact density and Pol II occupancy, independent of cohesin-basedloop extrusion. Through the development of a biophysical model integrating therole of transcription dynamics within a polymer model of chromosome organization,we demonstrate that Pol II-mediated attractive interactions with limited valencybetween transcribed regions yield quantitative predictions consistent withchromosome-conformation-capture and live-imaging experiments. Our work providescompelling evidence that transcriptional activity shapes the 4D genome throughPol II-mediated micro-compartmentalization.
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