TY - JOUR T1 - Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding JF - bioRxiv DO - 10.1101/2021.11.02.466589 SP - 2021.11.02.466589 AU - Mattia Conte AU - Ehsan Irani AU - Andrea M. Chiariello AU - Alex Abraham AU - Simona Bianco AU - Andrea Esposito AU - Mario Nicodemi Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/11/02/2021.11.02.466589.abstract N2 - Loop-extrusion and phase-separation have been proposed as mechanisms that shape chromosome large-scale spatial organization. It is unclear, however, how they perform relative to each other in explaining chromatin architecture data and whether they compete or co-exist at the single-molecule level. Here, we compare models of polymer physics based on loop-extrusion and phase-separation, as well as models where both mechanisms act simultaneously in a single molecule, against multiplexed FISH data available in human loci in IMR90 and HCT116 cells. We find that the different models recapitulate bulk Hi-C and average microscopy data. Single-molecule chromatin conformations are also well captured, especially by phase-separation based models that better reflect the experimentally reported segregation in globules of the considered genomic loci and their cell-to-cell structural variability. Such a variability is consistent with two main concurrent causes: single-cell epigenetic heterogeneity and an intrinsic thermodynamic conformational degeneracy of folding. Overall, the model combining loop-extrusion and polymer phase-separation provides a very good description of the data, particularly higher-order contacts, showing that the two mechanisms can co-exist in shaping chromatin architecture in single cells.Competing Interest StatementThe authors have declared no competing interest. ER -