Nuclear lamina-associated domain biogenesis is regulated by nuclear pore density during embryogenesis and mediates UV protection

Abstract

Lamina-associated domains (LADs) are critical for genome organization and function, but their formation during development is not well understood. Here, we use DamID and image analysis to reveal the dynamics of LAD biogenesis during C. elegans embryogenesis. At early stages, DNA at the lamina is transcriptionally active and lacks lamina-associated heterochromatin. This state depends on abundant nuclear pores, which prevent heterochromatin accumulation at the nuclear periphery. As development proceeds, pore numbers decline, enabling heterochromatin to access the lamina. Reducing nuclear-pore components induces precocious accumulation of heterochromatin to the lamina. Functionally, we find that heterochromatic LADs confer protection against ultraviolet (UV) radiation. Older embryos are resistant to UV light and concentrate DNA damage at the nuclear periphery, whereas early embryos are UV sensitive and accumulate damage throughout nuclei when unshielded by their mothers in utero. These findings identify embryonic dissipation of nuclear pores as a key step in heterochromatic LAD assembly, allowing older embryos to withstand exposure to UV irradiation.