Revealing the biophysics of lamina-associated domain formation by integrating theoretical modeling and high-resolution imaging.

ABSTRACT: Chromatin-lamina interactions regulate gene activity by forming lamina-associated domains (LADs), which contribute to cellular identity through gene repression. However, the strength of these interactions and their responsiveness to environmental cues remain unclear. Here, we develop a theoretical framework to predict LAD morphology in human mesenchymal stem cells (MSCs), whose differentiation potential depends on the stiffness of the microenvironment. Our model integrates chromatin-lamina interactions with histone modifications, revealing a bimodal distribution of chromatin-lamina affinity shaped by nuclear heterogeneities such as nuclear pores. We predict that contractility-driven translocation of histone deacetylase 3 (HDAC3) enhances chromatin-lamina affinity, leading to LAD thickening

SUBMITTER: Dhankhar M 

PROVIDER: S-EPMC12378204 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature