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

• Published in: Nature communications Vol. 10; no. 1; pp. 2771 - 13
• Main Authors: Khanna, Nimish, Zhang, Yaojun, Lucas, Joseph S, Dudko, Olga K, Murre, Cornelis
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 24.06.2019; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Antibodies; B-Lymphocytes - metabolism; Cell Line; Chains; Chromatin; Chromatin - metabolism; Chromosomes; Chromosomes - genetics; Chromosomes - metabolism; Configurations; Crosslinking; DNA-Binding Proteins - deficiency; Gene expression; Gene Expression Regulation - physiology; Genes, Immunoglobulin - genetics; Genomics; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - metabolism; Immunoglobulin Variable Region - genetics; Immunoglobulin Variable Region - metabolism; Lymphocytes; Lymphocytes B; Mice; Phase Transition; Phase transitions; Recombination; Segments; Sol-gel processes; V(D)J Recombination - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10628-9

Diverse antibody repertoires are generated through remote genomic interactions involving immunoglobulin variable (V ), diversity (D ) and joining (J ) gene segments. How such interactions are orchestrated remains unknown. Here we develop a strategy to track V -D J motion in B-lymphocytes. We find that V and D J 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 -D J 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.