Abstract
The extremely high concentration of macromolecules in a eukaryotic cell nucleus indicates that the nucleoplasm is a crowded macromolecular solution in which large objects tend to gather together due to crowding forces. It has been shown experimentally that crowding forces support the integrity of various nuclear compartments. However, little is known about their role in control of chromatin dynamics in vivo. Here, we experimentally addressed the possible role of crowding forces in spatial organization of the eukaryotic genome. Using the mouse β-globin domain as a model, we demonstrated that spatial juxtaposition of the remote regulatory elements of this domain in globin-expressing cells may be lost and restored by manipulation of the level of macromolecular crowding. In addition to proving the role of crowding forces in shaping interphase chromatin, our results suggest that the folding of the chromatin fiber is a major determinant in juxtaposing remote genomic elements.
Highlights
It has become increasingly evident that an apparent order in the eukaryotic cell nucleus originates out of disorder because of the self-assembly of functional nuclear compartments, which can be initiated by various “seeding events” including realization of functional processes [1,2,3,4,5,6]
Using cultured mouse erythroid cells as a model, we demonstrated that a decrease in the level of macromolecular crowding results in a significant loss of interaction between the components of β-globin domain active chromatin hub (ACH), which is indicated by a decrease in the level of the chromosome conformation capture (3C) signal
In all of the experiments, we used induced cultured mouse erythroid cells. This model was chosen because we aimed to study the configuration of the β-globin ACH
Summary
It has become increasingly evident that an apparent order in the eukaryotic cell nucleus originates out of disorder because of the self-assembly of functional nuclear compartments, which can be initiated by various “seeding events” including realization of functional processes [1,2,3,4,5,6] The integrity of these compartments (such as nucleoli, Cajal bodies, and PML bodies) is supported by weak specific interactions and non-specific entropic forces (in particular, by “depletion attraction forces” [4, 7, 8]) that originate in crowded macromolecular solutions [9,10,11,12]. It has PLOS ONE | DOI:10.1371/journal.pone.0139855 October 5, 2015
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