Nucleus size and its effect on nucleosome stability in living cells.

Abstract

Spatial conformation of chromatin in eukaryotic cells is mainly determined by an intricate interplay between the DNA-binding properties of architectural proteins and physical constraints imposed on chromosomal DNA by a tight nuclear space. Yet, the exact effect of the nucleus size on DNA-protein interactions and chromatin structure currently remains obscure. Furthermore, there is even no clear understanding of molecular mechanisms responsible for the nucleus size regulation in living cells. In our study, we analyse the relative contribution of several key components of living cells to the regulation of the nucleus size through direct application of pressure on the nuclear envelope. It is shown that the nucleus size in higher eukaryotes is mainly defined by the difference between the surface tensions of the nuclear envelope and the endoplasmic reticulum membrane as well as the osmotic pressure exerted by cytosolic macromolecules on the nucleus. In addition, calculations demonstrate that the cell nucleus functions as a piezoelectric element, changing its electrostatic potential in a size-dependent manner. This effect has been found to have a profound impact on stability of nucleosomes, revealing a previously unknown link between the nucleus size and chromatin structure. Overall, our study provides new insights into the molecular mechanisms responsible for regulation of the nucleus size, as well as the potential role of nuclear organization in shaping the cell response to environmental cues.