A polymer model explains the complexity of large-scale chromatin folding

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Abstract

The underlying global organization of chromatin within the cell nucleus has been the focus of intense recent research. Hi-C methods have allowed for the detection of genome-wide chromatin interactions, revealing a complex largescale organization where chromosomes tend to partition into megabase-sized “topological domains” of local chromatin interactions and intra-chromosomal contacts extends over much longer scales, in a cell-type and chromosome specific manner. Until recently, the distinct chromatin folding properties observed experimentally have been difficult to explain in a single conceptual framework. We reported that a simple polymer-physics model of chromatin, the strings and binders switch (SBS) model, succeeds in describing the full range of chromatin configurations observed in vivo. The SBS model simulates the interactions between randomly diffusing binding molecules and binding sites on a polymer chain. It explains how polymer architectural patterns can be established, how different stable conformations can be produced and how conformational changes can be reliably regulated by simple strategies, such as protein upregulation or epigenetic modifications, via fundamental thermodynamics mechanisms.

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