The "nuclear physics" behind epigenetic control of cell fate

It is well understood that replicative and transcriptional responses in the nucleus occur under the influence of specific extracellular biochemical signals (e.g. growth factors and cytokines). However, it has become apparent recently that the nucleus is also able to sense and respond to more generic cues, such as physical forces and mechanical constraints. Indeed, being the largest and stiffest intracellular organelle, the nucleus is exposed to various types of forces acting from inside and outside the cell. These forces result in global and local deformations of the nucleus, which can significantly affect spatial organization and mechanical state of the nuclear envelope (NE). Considering that peripheral chromatin is attached to the NE, forces applied to the NE are transmitted to chromatin. This, in turn, can impact chromatin organization, dynamics, and activity. Where do these forces originate from and what are the physiological contexts in which they modulate critical nuclear activities? Discussing these questions is the main goal of the present mini-review.