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

Nimish Khanna, Yaojun Zhang, Joseph S. Lucas, Olga K. Dudko () and Cornelis Murre ()
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Nimish Khanna: University of California, San Diego
Yaojun Zhang: Princeton University
Joseph S. Lucas: University of California, San Diego
Olga K. Dudko: University of California, San Diego
Cornelis Murre: University of California, San Diego

Nature Communications, 2019, vol. 10, issue 1, 1-13

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

Date: 2019
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DOI: 10.1038/s41467-019-10628-9

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