Taming active transposons at Drosophila telomeres: The interconnection between HipHop’s roles in capping and transcriptional silencing

Abstract

Drosophila chromosomes are elongated by retrotransposon attachment, a process poorly understood. Here we characterized a mutation affecting the HipHop telomere-capping protein. In mutant ovaries and the embryos that they produce, telomere retrotransposons are activated and transposon RNP accumulates. Genetic results are consistent with that this hiphop mutation weakens the efficacy of HP1-mediated silencing while leaving piRNA-based mechanisms largely intact. Remarkably, mutant females display normal fecundity suggesting that telomere de-silencing is compatible with germline development. Moreover, unlike prior mutants with overactive telomeres, the hiphop stock does not over-accumulate transposons for hundreds of generations. This is likely due to the loss of HipHop’s abilities both to silence transcription and to recruit transposons to telomeres in the mutant. Furthermore, embryos produced by mutant mothers experience a checkpoint activation, and a further loss of maternal HipHop leads to end-to-end fusion and embryonic arrest. Telomeric retroelements fulfill an essential function yet maintain a potentially conflicting relationship with their Drosophila host. Our study thus showcases a possible intermediate in this arm race in which the host is adapting to over-activated transposons while maintaining genome stability. Our results suggest that the collapse of such a relationship might only occur when the selfish element acquires the ability to target non-telomeric regions of the genome. HipHop is likely part of this machinery restricting the elements to the gene-poor region of telomeres. Lastly, our hiphop mutation behaves as a recessive suppressor of PEV that is mediated by centric heterochromatin, suggesting its broader effect on chromatin not limited to telomeres. Transposons are selfish elements that multiply by inserting extra copies of themselves into the host genome. Active transposons thus threaten the stability of the host genome, while the host responses by transcriptionally silencing the selfish elements or targeting their insertions towards gene-poor regions of the genome. Chromosome ends (telomeres) in the fruit fly Drosophila are elongated by active transposition of retrotransposons. Although much is known about how these elements are silenced, little is known about the remarkable accuracy by which they are targeted to telomeres. Prime candidates through which the host mounts such defenses are members of the protein complexes that protect telomeres. Here we characterized a hypomorphic mutation of the HipHop protein, and showed that active telomeric transcription in the mutant germline persists for generations without leading to runaway telomere elongation, that embryos laid by the mutant female suffer rampant end-to-end fusions, and that telomeric targeting of the transposon machinery is defective in the mutant soma. Collectively our data suggest that HipHop is essential for preventing telomere fusions, silencing telomeric transposons, and recruiting transposon machinery to telomeres. Our study thus identifies a factor essential for the host control over active transposons and a paradigm for studying such control mechanisms.