Mature chromatin packing domains persist after RAD21 depletion in 3D.

Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.

Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system.

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion.

Local volume concentration, packing domains, and scaling properties of chromatin.

We propose the Self Returning Excluded Volume (SR-EV) model for the structure of chromatin based on stochastic rules and physical interactions. The SR-EV generate conformationally defined domains observed by single-cell imaging techniques. From nucleosome to chromosome scales, the model captures the overall chromatin organization as a corrugated system, with dense and dilute regions alternating in a manner that resembles the mixing of two disordered bi-continuous phases.

Local Volume Concentration, Packing Domains and Scaling Properties of Chromatin.

We propose the Self Returning Excluded Volume (SR-EV) model for the structure of chromatin based on stochastic rules and physical interactions. The SR-EV generate conformationally-defined domains observed by single cell imaging techniques. From nucleosome to chromosome scales, the model captures the overall chromatin organization as a corrugated system, with dense and dilute regions alternating in a manner that resembles the mixing of two disordered bi-continuous phases.

Local Volume Concentration, Packing Domains and Scaling Properties of Chromatin.

We propose the Self Returning Excluded Volume (SR-EV) model for the structure of chromatin based on stochastic rules and physical interactions that is able to capture the observed behavior across imaging and sequencing based measures of chromatin organization. The SR-EV model takes the return rules of the Self Returning Random Walk, incorporates excluded volume interactions, chain connectivity and expands the length scales range from 10 nm to over 1 micron. The model is computationally fast and we created thousands of configurations that we grouped in twelve different ensembles according to the two main parameters of the model.