Multi-tissue proteomics identifies a link between satellite DNA organization and transgenerational transposon repression inDrosophila

Abstract

ABSTRACTThe pericentromeric heterochromatin of eukaryotic chromosomes primarily consists of abundant non-coding repeats known as satellite DNA, which promote accurate chromosome segregation and genome stability. During interphase, sequence-specific satellite DNA-binding proteins cluster repeats from multiple chromosomes into foci known as chromocenters, which function to encapsulate the entire genome in a single nucleus. Despite the pivotal role of satellite DNA-binding proteins and chromocenters in cellular function, the proteins associated with these repetitive sequences remains incompletely characterized. Here, we use quantitative mass spectrometry to characterize the chromocenter-associated proteome inDrosophilaembryos, ovaries and testes using two satellite DNA-binding proteins, D1 and Prod, as baits. We identify nearly 500 interactions, including known heterochromatin-associated proteins as well as proteins previously unlinked to satellite DNA or chromocenters. Among these interactions, we find that multiple components of the transposon-silencing piRNA pathway are associated with chromocenters. Strikingly, we reveal that proper satellite DNA clustering plays a role in transgenerational transposon repression, such that mothers with disrupted chromocenters give rise to progeny that exhibit transposon de-repression, germ cell loss and gonadal atrophy. Overall, our study highlights a novel link between satellite DNA repeats and transposon repression and lays the foundation for a more comprehensive understanding of satellite DNA function across tissues.