Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization

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 Hi-C and live-imaging experiments. Our work provides compelling evidence that transcriptional activity shapes the 4D genome through Pol II-mediated micro-compartmentalization.

The genome in space and time comes of age

“…Pol 2 occupancy appears as a key determinant of gene folding through phase separation. Interestingly, the speaker suggested that Pol 2-mediated condensation, coupled with transcriptional bursting, may slow down gene mobility, aligning with Bystricky’s observations [ 27 ].…”

Deciphering histone mark-specific fine-scale chromatin organization at high resolution with Micro-C-ChIP

“…One-sided halt or pause of loop-extrusion leads to the emergence of stripes in interaction heatmaps 13,35 . It is demonstrated that the strength of stripe features correlates with transcription rates and RNAPII occupancy at promoters 1,48 . Here, we demonstrate that the H3K27me3-marked promoters that are depleted for RNAPII display stripe formation in mESC.…”