Repetitive sequences derived from transposons make up a large fraction of the genome and must be silenced to protect genome integrity. Silencing of these elements is especially important in the germ line, where the piRNA pathway has been shown to be involved. Repeats are often found in heterochromatin, which in C. elegans are regions dispersed over the chromosome arms, however the roles and interactions of heterochromatin proteins are poorly understood. We have shown that a diverse set of heterochromatin factors act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2 and the H2K9me2 histone methyltransferase MET-2/SETDB1 show genome-wide co-binding and enrichment at repetitive elements, and mutants show a derepression of a subset of transposons. Furthermore, heterochromatin mutants are characterized by functionally redundant and temperature sensitive sterility, and display increased germline apoptosis and activation of DNA damage signalling. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting expression of MIRAGE1 DNA transposons or endogenous meiotic double strand breaks. Loss of CEP-1/p53 also ameliorates both their fertility and somatic defects, suggesting that DNA damage signalling contributes to the phenotypes observed. Through genetics and transcriptional profiling, we uncovered complex interactions between heterochromatin factors and the piRNA and nuclear RNAi pathways, including functional redundancy in repetitive element repression between
let-418 and
nrde-2. This redundancy underlies the importance of safeguarding the genome through multiple means. It is also becoming evident that heterochromatic silencing occurs through different mechanisms at different genomic elements. We are currently dissecting interactions between the various factors, as well as H3K9me2/3, to uncover their mechanisms of action at heterochromatic regions, as well as investigating their roles in development and adult homeostasis.