ИСТИНА

Nuclear lamina (NL) is a meshwork of lamins and lamin-associated proteins lining the nuclear envelope (NE). Chromatin adjoining NL in the lamina-associated domains (LADs) is densely packed and contains predominantly silent genes. However, how NL impacts the global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to the bulk chromatin compactization and repositioning from the NE. This increases the chromatin density in the topologically-associating domains (TADs) harboring active genes, and enhances the inter-TAD interactions resulting in the intermingling of active and inactive chromatin compartments. Importantly, upon NL disruption, a fraction of TADs strongly overlapping with LADs becomes less compact, while the genes residing there are derepressed. Two-color FISH confirms a more decompacted state of a TAD after its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact the attached TADs. Collectively, our findings demonstrate a dual function of NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.