Telomere proteins protect the ends of linear chromosomes from shortening during cell replication. Deficiency for telomerase results in loss of telomeric sequence across multiple generations. However, there is no described role for telomeres in transgenerational epigenetic inheritance. The C. elegans Pot1 homologues POT-1 and POT-2, members of the shelterin complex, form foci at telomeres in germ cells. These foci disappear by fertilization and gradually accumulate during early development. We find that mutation of either Pot1 gene in sperm or oocytes alters levels of telomeric foci for multiple generations, despite progeny possessing wild-type Pot1 genes.
pot-2 mutant gametes gave rise to progeny with abundant POT-1::mCherry and mNeonGreen::POT-2 foci during early development, an effect which persisted for six generations. In contrast,
pot-1 mutant gametes gave rise to progeny with fewer foci for several generations. We investigated a range of genes involved in epigenetic inheritance. While Pot1 foci were not affected by loss of genes involved in sRNA pathways, they were greatly diminished for at least two generations by the loss of MET-2, SET-25, or SET-32, three methyltransferases that promote heterochromatin formation. We propose that POT proteins may interact with H3K9 methyltransferases during gametogenesis to induce a persistent form of transgenerational epigenetic inheritance that influences telomeric heterochromatin.