A membrane-associated condensate drives paternal epigenetic inheritance inC. elegans

SUMMARY Transgenerational epigenetic inheritance (TEI) describes the transmission of gene-regulatory information across generations without altering DNA sequences, and allows priming of offspring towards transposable elements (TEs) and changing environmental conditions. One important mechanism that acts in TEI is based on small non-coding RNAs. Whereas factors for maternal inheritance of small RNAs have been identified, paternal inheritance is poorly understood, as much of the cellular content is extruded during spermatogenesis. We identify a phase separation-based mechanism, driven by the protein PEI-1, which is characterized by a BTB-BACK domain and an intrinsically disordered region (IDR). PEI-1 specifically secures the Argonaute protein WAGO-3 within maturing sperm in C. elegans . Localization of PEI granules in mature sperm is coupled, via S-palmitoylation, to myosin-driven transport of membranous organelles. pei-1 -like genes are also found in human and often expressed in testis, suggesting that the here identified mechanism may be broadly conserved.