Eukaryotic cells have a layer of heterochromatin at the nuclear periphery. To investigate mechanisms regulating chromatin distribution, we analyzed heterochromatin organization in different tissues and species, including mice with mutations in the lamin B receptor (Lbr) and lamin A (Lmna) genes that encode nuclear envelope (NE) proteins. We identified LBR- and lamin-A/C-dependent mechanisms tethering heterochromatin to the NE. The two tethers are sequentially used during cellular differentiation and development: first the LBR- and then the lamin-A/C-dependent tether. The absence of both LBR and lamin A/C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior. Myoblast transcriptome analyses indicated that selective disruption of the LBR- or lamin-A-dependent heterochromatin tethers have opposite effects on muscle gene expression, either increasing or decreasing, respectively. These results show how changes in NE composition contribute to regulating heterochromatin positioning, gene expression, and cellular differentiation during development.

Background: The unusual nuclear shape of neutrophils has been speculated to facilitate their passage through confined spaces. Results: Levels of nuclear protein lamin A modulate cell passage through micron-scale pores. Conclusion:The unique protein composition of neutrophil nuclei facilitates their deformation; lobulated nuclear shape is not essential. Significance: Altered nuclear envelope composition, as reported in cancer cells, could impact cell passage through physiological gaps.

The nuclear pore complex (NPC) is the sole gateway between the nucleus and the cytoplasm. NPCs fuse the inner and outer nuclear membranes to form aqueous translocation channels that allow the free diffusion of small molecules and ions, as well as receptor-mediated transport of large macromolecules. The NPC regulates nucleocytoplasmic transport of macromolecules, utilizing soluble receptors that identify and present cargo to the NPC, in a highly selective manner to maintain cellular functions. The NPC is composed of multiple copies of approximately 30 different proteins, termed nucleoporins, which assemble to form one of the largest multiprotein assemblies in the cell. In this review, we address structural and functional aspects of this fundamental cellular machinery.