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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.

SUBMITTER: Khanna N

PROVIDER: S-EPMC6591236 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Khanna Nimish N Zhang Yaojun Y Lucas Joseph S JS Dudko Olga K OK Murre Cornelis C

Nature communications 20190624 1

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 spatia ...[more]

PMID: 31235807

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Project description:Advances in supramolecular assembly have enabled the design and synthesis of functional materials with well-defined structures across multiple length scales. Biopolymer-synthetic hybrid materials can assemble into supramolecular structures with a broad range of structural and functional diversity through precisely controlled noncovalent interactions between subunits. Despite recent progress, there is a need to understand the mechanisms underlying the assembly of biohybrid/synthetic molecular building blocks, which ultimately control the emergent properties of hierarchical assemblies. In this work, we study the concentration-driven self-assembly and gelation of π-conjugated synthetic oligopeptides containing different π-conjugated cores (quaterthiophene and perylene diimide) using a combination of particle tracking microrheology, confocal fluorescence microscopy, optical spectroscopy, and electron microscopy. Our results show that π-conjugated oligopeptides self-assemble into β-sheet-rich fiber-like structures at neutral pH, even in the absence of electrostatic screening of charged residues. A critical fiber formation concentration cfiber and a critical gel concentration cgel are determined for fiber-forming π-conjugated oligopeptides, and the linear viscoelastic moduli (storage modulus G' and loss modulus G″) are determined across a wide range of peptide concentrations. These results suggest that the underlying chemical structure of the synthetic π-conjugated cores greatly influences the self-assembly process, such that oligopeptides appended to π-conjugated cores with greater torsional flexibility tend to form more robust fibers upon increasing peptide concentration compared to oligopeptides with sterically constrained cores. Overall, our work focuses on the molecular assembly of π-conjugated oligopeptides driven by concentration, which is controlled by a combination of enthalpic and entropic interactions between oligopeptide subunits.

Dataset Information

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

Publications

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

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