Changes in Chromatin Organisation and Mechanotransduction Mediated by Mutant Lamins in Laminopathies

The filamentous nuclear lamina network is predominantly made up of lamin proteins, which play pivotal roles in maintaining nuclear architecture, chromatin structure, mechanotransduction and various other nuclear processes. Among the lamin proteins, A type is the principal mechanical component of the nucleus and controls gene expression via direct interactions with chromatin and chromatin modulator proteins. Mutations in the LMNA gene cause a plethora of diseases termed laminopathies, including various cardiac and muscular ailments, by disrupting nuclear integrity and mechanotransduction signalling. These mutations also alter chromatin organisation and epigenetic landscape, tantamount to compromised cellular homeostasis. In this chapter, we elaborate on lamin A's molecular structure, assembly dynamics and its role in nuclear mechanotransduction and chromatin maintenance. Additionally, we highlighted the pathological consequences of lamin A dysfunction and discussed emerging approaches aimed at rationalising the cellular- and tissue-specific effects during laminopathies.