The Force is Strong with This Epigenome: Chromatin Structure and Mechanobiology

All life forms sense and respond to mechanical stimuli. Throughout evolution, organisms develop diverse mechanosensing and mechanotransduction pathways, leading to fast and sustained mechanoresponses. Memory and plasticity characteristics of mechanoresponses are thought to be stored in the form of epige-netic modifications, including chromatin structure alterations. These mechanoresponses in the chromatin context share conserved principles across species, such as lateral inhibition during organogenesis and development. However, it remains unclear how mechanotransduction mechanisms alter chromatin structure for specific cellular functions, and if altered chromatin structure can mechanically affect the envi-ronment. In this review, we discuss how chromatin structure is altered by environmental forces via an outside-in pathway for cellular functions, and the emerging concept of how chromatin structure alterations can mechanically affect nuclear, cellular, and extracellular environments. This bidirectional mechanical feedback between chromatin of the cell and the environment can potentially have important physiological implications, such as in centromeric chromatin regulation of mechanobiology in mitosis, or in tumor-stroma interactions. Finally, we highlight the current challenges and open questions in the field and pro-vide perspectives for future research.Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Automated summary

All life forms have the ability to sense and respond to mechanical stimuli through mechanotransduction pathways, leading to fast and sustained mechanoresponses. Mechanoresponses are stored as epigenetic modifications, including chromatin structure alterations. The mechanisms by which mechanotransduction alters chromatin structure and its effects on the cellular environment are still unclear.