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

Abstract

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_HJ_H motion in B-lymphocytes. We find that V_H and D_HJ_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_HJ_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.