Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions

N Khanna and YJ Zhang and JS Lucas and OK Dudko and C Murre, NATURE COMMUNICATIONS, 10, 2771 (2019).

DOI: 10.1038/s41467-019-10628-9

Diverse antibody repertoires are generated through remote genomic interactions involving immunoglobulin variable (V-H), diversity (D-H) and joining (J(H)) gene segments. How such interactions are orchestrated remains unknown. Here we develop a strategy to track V-H-D(H)J(H) motion in B-lymphocytes. We find that V-H and D(H)J(H) segments are trapped in configurations that allow only local motion, such that spatially proximal segments remain in proximity, while spatially remote segments remain remote. Within a subset of cells, however, abrupt changes in V-H-D(H)J(H) motion are observed, plausibly caused by temporal alterations in chromatin configurations. Comparison of experimental and simulated data suggests that constrained motion is imposed by a network of cross-linked chromatin chains characteristic of a gel phase, yet poised near the sol phase, a solution of independent chromatin chains. These results suggest that chromosome organization near the sol-gel phase transition dictates the timing of genomic interactions to orchestrate gene expression and somatic recombination.

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