Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization

• DOI: 10.1038/s41467-024-48698-z
• Publication Date: 2024-05-21T18:02:16Z
• Authors: Aayush Kant; Zixian Guo; Vinayak Vinayak; Maria Victoria Ne...; Wing Shun Li; Vasundhara Agrawal; Emily Pujadas; Luay Almassalha; Vadim Backman; Melike Lakadamyali; Maria Pia Cosma; Vivek B. Shenoy
• Keywords: Transcription; Epigenesis

Abstract In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, modifications, extrusion. predict that heterochromatic governed by balance among diffusive flux methylated histones sustaining them acetylation reactions in process loop extrusion via supercoiling RNAPII at their periphery, which contributes to reduction. Super-resolution nano-imaging five distinct cell lines confirm predictions indicating absence leads larger heterochromatin domains. Furthermore, accurately reproduces findings regarding how transcription-mediated loss can mitigate impacts excessive cohesin loading. Our shed light role genome organization, offering insights into dynamics potential therapeutic targets.