2026/03/27 by Kaitlyn M Shen, Emily J. Shields, Vasia Barka +12 · 2 voices
Biochemistry, Genetics and Molecular Biology · #Nuclear Structure and Function #Skin and Cellular Biology Research #Genomics and Chromatin Dynamics
paper · doi:10.1083/jcb.202506137
openalex publication_date 2026/03/27 · openalex created_date 2026/03/28 · openalex updated_date 2026/07/16
The spatial organization of chromatin at the nuclear lamina contributes to genome structure and gene regulation. Mechanical inputs are increasingly recognized as key regulators of nuclear architecture, and understanding how they control genome-lamina interactions and influence diseases associated with the nuclear lamina remains unclear. To understand the role of lamin proteins and the cytoskeleton in peripheral chromatin organization and consider this role in the context of laminopathies, we performed siRNA-mediated partial knockdown of lamin A/C (LMNA) in human cardiomyocytes and examined lamina-associated domains (LADs). Genome-wide mapping and locus-specific imaging reveal that LADs with a distinct molecular signature are preferentially vulnerable to LMNA reduction. A subset of these sensitive LADs retain lamina association when the linker of nucleoskeleton and cytoskeleton complex (LINC) is disrupted or microtubules are depolymerized. These findings indicate that, in the context of a compromised nuclear lamina, cytoskeletal inputs transmitted through the LINC complex play a key role in the reorganization of peripheral chromatin.