Effects of chromatin-lamina attachment on extra-long-range chromatin interactions.

The three-dimensional (3D) organization of the genome is strongly influenced by interactions between chromatin and lamin proteins at the nuclear envelope. Here, we investigate the role of lamina-associated domains (LADs) in shaping genome architecture using coarse-grained polymer models of mouse embryonic fibroblasts and embryonic stem cells. By integrating genome-wide LAD maps from DamID assays, we simulate chromatin conformations with and without LAD attachment. Incorporating LAD-lamina interactions reproduces the experimentally observed radial chromatin distribution and reveals that LADs induce extensive long-range (70-120 Mbp) chromatin contacts beyond typical loops and topologically associating domains (TADs). We describe these contacts in terms of two limiting geometric scenarios: LAD crowding, in which peripheral tethering increases the proximity of nearby non-LAD regions to LADs, and LAD anchoring, in which lamina-bound LADs constrain neighboring chromatin positions. LAD-induced interactions were especially prominent in chromatin regions lacking architectural proteins, such as CTCF, and were associated with lower gene density and reduced transcriptional activity. Together, these results suggest that LAD-lamina tethering reshapes long-range chromatin contact probabilities through boundary-driven effects and is associated with gene-poor, less transcriptionally active chromatin regions.