On the Border of Order: Chromosomal Organization in Space and Time*

Many biological processes, from antibody production to tissue differentiation, share a common fundamental step — establishing a physical contact between distant genomic segments. How do remote segments find each other on a remarkably short timescale despite being strung out over millions of base pairs along the DNA? What is the mechanism of the high degree of orchestration of remote genomic interactions? We address these questions in the context of adaptive immunity – the system that enables the individual to respond to a great variety of pathogens through a diverse repertoire of antibodies. Experimental data from live-cell imaging in B-lymphocytes reveal the signatures of anomalous diffusion that help us identify the dominant mechanism of genomic motion. Comparison of experimental and simulated data, along with insights from polymer physics, suggest that an interphase chromosome behaves as a network of cross-linked chains characteristic of a gel phase, yet it is poised near the sol phase, a solution of independent chains. Chromosome organization near the phase boundary provides the genome with a tradeoff between stability and responsiveness and orchestrates the timing of genomic interactions.