Chromatin remodelling: a driving force in reverse mechanotransduction

Chromatin serves as the dynamic carrier of genetic and epigenetic information in eukaryotic cells, playing a pivotal role in maintaining nuclear shape, mechanical stability, and cellular function. Aberrant nuclear morphology, often observed in mechanically stressed environments or diseases such as progeria and muscular dystrophy, correlates with nuclear dysfunction, DNA damage, and disrupted mechanotransduction. Chromatin exists in two main configurations - compacted heterochromatin and decompacted euchromatin - each regulating gene expression and cellular behaviour through epigenetic modifications. Histone acetyltransferases and deacetylases modulate chromatin compaction, while histone methylation introduces further regulatory complexity. Chromatin's viscoelastic properties enable it to store and restore mechanical energy, acting as a mechanosensitive component within the nucleus. External forces propagate from the extracellular matrix through focal adhesions, the cytoskeleton, and the nuclear lamina to chromatin, forming a direct mechanotransduction pathway. However, the reverse pathway - how internal nuclear forces generated during chromatin remodelling influence the nuclear membrane, cytoskeleton, and cell adhesion - remains poorly understood. This review explores the role of chromatin as a tensegrity element, capable of generating mechanical forces through condensate formation. It examines evidence supporting chromatin decompaction as a regulator of reverse mechanotransduction and identifies potential mechanical partners involved in this process. Understanding these mechanisms may elucidate how chromatin dynamics contribute to cellular fate decisions and disease pathogenesis.