In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence of transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, histone modifications, and chromatin extrusion. We predict that the size of heterochromatic domains is governed by a balance among the diffusive flux of methylated histones sustaining them and the acetylation reactions in the domains and the process of loop extrusion via supercoiling by RNAPII at their periphery, which contributes to size reduction. Super-resolution and nano-imaging of five distinct cell lines confirm the predictions indicating that the absence of transcription leads to larger heterochromatin domains. Furthermore, the model accurately reproduces the findings regarding how transcription-mediated supercoiling loss can mitigate the impacts of excessive cohesin loading. Our findings shed light on the role of transcription in genome organization, offering insights into chromatin dynamics and potential therapeutic targets.
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Abstract Free, publicly-accessible full text available December 1, 2025 -
Akbari, Ehsan ; Park, Eui-Jin ; Singh, Ajit K. ; Vinayak, Vinayak ; Virk, Ranya K. ; Wereszczynksi, Jeff ; Musselman, Catherine A. ( , Biophysical Reviews)The MGO symposium was held on February 18th with seven featured speakers from all over the globe. Drs. Bin Zhang and Alexey Onufriev chaired the session with Drs. Yamini Dalal and Anna Panchenko as the 2022 MGO co-chairs. The session and goals of the MGO subgroup were introduced by Dr. Panchenko, followed by talks from the invited speakers. The presentations showcased research at the forefront of the field and elicited high audience engagement. Here, we summarize the presentations of these invited speakers.more » « less