Effects of forces on chromatin

Abstract

Chromatin is a unique structure of DNA and histone proteins in the cell nucleus and the site of dynamic regulation of gene expression. Soluble factors are known to affect the chromatin structure and function via activating or inhibiting specific transcription factors. Forces on chromatin come from exogenous stresses on the cell surface and/or endogenous stresses, which are regulated by substrate mechanics, geometry, and topology. Forces on chromatin involve direct (via adhesion molecules, cytoskeleton, and the linker of nucleoskeleton and cytoskeleton complexes) and indirect (via diffusion and/or translocation processes) signaling pathways to modulate levels of chromatin folding and deformation to regulate transcription, which is controlled by histone modifications and depends on magnitude, direction, rate/frequency, duration, and modes of stresses. The rapid force transmission pathway activates multiple genes simultaneously, and the force may act like a "supertranscription factor." The indirect mechanotransduction pathways and the rapid force transmission pathway together exert sustained impacts on the chromatin, the nucleus, and cell functions.