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

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.