Dynamic asymmetry and why chromatin defies simple physical definitions
Introduction
The eukaryotic nucleus is a wild tangle of protein and nucleic acid, overflowing in activity. However, despite its chaotic appearance, the business of the nucleus is readily accomplished. In part, this is achieved by dynamically organizing chromatin into domains that possess distinct biophysical properties, enable specific biochemical activities, and have the versatility to change throughout development and in response to the environment. Here, I discuss some new insights into the physical consequences of dynamic chromatin organization.
Section snippets
Chromatin organization
In essence, chromatin is DNA wrapped around histone proteins [1]. But, there is also a host of other proteins and RNA associated with chromatin that can be considered integral to the chromatin ultrastructure [2, 3, 4]. However, unlike DNA and histones, most chromatin-associated proteins are incredibly dynamic, perhaps bound only transiently to any other molecules comprised within the chromatin fiber [5, 6, 7]. Remarkably, these dynamic proteins establish and maintain a stable, reproducible
Chromatin phase separation
Formally, the question of whether chromatin is organized into phase-separated domains is somewhat ill-posed. Undoubtedly, distinct regions of chromatin fibers exist in separate nuclear compartments, but by virtue of being—at least in principle—a single entity, it is probably inappropriate to refer to different regions of a continuous polymer as phase separated from itself. However, a single chromatin fiber may traverse and/or induce the formation of several distinct phase-separated domains as
Viscoelastic phase separation of HP1α-DNA condensates
The most straightforward example of a chromatin domain is constitutive heterochromatin. This type of chromatin is characterized by a dense appearance that preferentially localizes to the nuclear periphery and is bound by members of the Heterochromatin Protein 1 (HP1) family [11,12,62]. In mammals, HP1α is critical for condensing and positioning heterochromatin [63,64]. Recently, it was shown that HP1α undergoes phase separation when it is phosphorylated or mixed with DNA [34,65]. Furthermore,
Consequences of viscoelastic phase separation and dynamic asymmetry
What conclusions or insights can be taken away from conceptualizing chromatin as we have here: a polymer gel embedded in proteinaceous liquid that collectively behaves viscoelastically? First of all, it is worth noting that many of the advantages of LLPS are still true of these condensates, such as concentrating effects, self-assembly, and curated local environments [43,44]. However, in contrast to liquids, a viscoelastic material can respond in opposition to mechanical stresses (Figure 3).
Conflict of interest statement
The authors declare no conflict of interests.
Acknowledgements
Support to SR through the UCSF Program for Breakthrough Biomedical Research (PBBR) and Sandler Foundation.
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