Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation.

ABSTRACT: The spatial organization of chromosomes has key functional roles, yet how chromosomes fold remains poorly understood at the single-molecule level. Here, we employ models of polymer physics to investigate DNA loci in human HCT116 and IMR90 wild-type and cohesin depleted cells. Model predictions on single-molecule structures are validated against single-cell imaging data, providing evidence that chromosomal architecture is controlled by a thermodynamics mechanism of polymer phase separation whereby chromatin self-assembles in segregated globules by combinatorial interactions of chromatin factors that include CTCF and cohesin. The thermodynamics degeneracy of single-molecule conformations results in broad structural and temporal variability of TAD-like contact patterns. Globules establish sta

SUBMITTER: Conte M 

PROVIDER: S-EPMC7335158 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature