Abstract
Although our understanding of the involvement of heterochromatin architectural factors in shaping nuclear organization is improving, there is still ongoing debate regarding the role of active genes in this process. In this study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate the relationship between gene transcription and 3D gene folding. Our analysis uncovers a nonmonotonic - globally positive - correlation between intragenic contact density and Pol II occupancy, independent of cohesin-based loop extrusion. Through the development of a biophysical model integrating the role of transcription dynamics within a polymer model of chromosome organization, we demonstrate that Pol II-mediated attractive interactions with limited valency between transcribed regions yield quantitative predictions consistent with chromosome-conformation-capture and live-imaging experiments. Our work provides compelling evidence that transcriptional activity shapes the 4D genome through Pol II-mediated micro-compartmentalization.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Briefly, our main revisions lie in (1) new data analysis (and corresponding figures) to compare intra-gene condensation to other epigenetic signals; (2) new simulations (and corresponding figures) to investigate more systematically the effect of non-uniform Pol II profiles and long-range contact between genes; (3) extensive editing of the text.