A DNA-containing phase-separated compartment links the nuclear envelope to chromosome axes to promote homolog pairing in C. elegans

Homologous chromosome pairing is a critical prerequisite for successful meiosis, yet the molecular mechanisms underlying this process remain elusive. In Caenorhabditis elegans, chromosome pairing centers (PCs) and PC-recruited proteins mediate homolog recognition and pairing. Here, we further dissect the molecular characteristics of this system and reveal the involvement of a phase-separated compartment in pairing. Focusing on the PC protein HIM-8, we explored its functional domains in vivo and its self-multimerizing properties in vitro. We find that the amino-terminal domain facilitates PC chromatin binding of the carboxyl-terminal domain, whereas the middle unstructured region is essential for PC association with the nuclear envelop (NE). Integrated analyses suggest that PC-NE association is mediated by a DNA-containing phase-separated compartment that is spatially distinct from, but connected to, the chromosome axis—likely through flexible linkages. We propose that homology evaluation occurs within this compartment, where direct DNA-DNA interactions could play a role.