Upon mating, females of many animal species undergo dramatic changes in their behavior. In Drosophila melanogaster, postmating behaviors are triggered by sex peptide (SP), which is produced in the male seminal fluid and transferred to female during copulation. SP modulates female behaviors via sex peptide receptor (SPR) located in a small subset of internal sensory neurons that innervate the female uterus and project to the CNS. Although required for postmating responses only in these female sensory neurons, SPR is expressed broadly in the CNS of both sexes. Moreover, SPR is also encoded in the genomes of insects that lack obvious SP orthologs. These observations suggest that SPR may have additional ligands and functions. Here, we identify myoinhibitory peptides (MIPs) as a second family of SPR ligands that is conserved across a wide range of invertebrate species. MIPs are potent agonists for Drosophila, Aedes, and Aplysia SPRs in vitro, yet are unable to trigger postmating responses in vivo. In contrast to SP, MIPs are not produced in male reproductive organs, and are not required for postmating behaviors in Drosophila females. We conclude that MIPs are evolutionarily conserved ligands for SPR, which are likely to mediate functions other than the regulation of female reproductive behaviors.Drosophila | female post-mating behavior | G protein-coupled receptor | neuropeptide | neuromodulation P eptide signaling through G protein-coupled receptors is a widely used mechanism for reversibly modulating the behavioral output of innate neural circuits (for review see ref. 1). A prominent example of peptidergic modulation of behavior is the regulation of female reproductive behavior in Drosophila melanogaster by the male's sex peptide (SP). SP is a small peptide present in the male seminal fluid. Upon mating, SP is transferred to the female, where it triggers dramatic changes in reproductive and other behaviors (2, 3). These behavioral modifications typically last for about a week, the period for which the female is able to store and use sperm from the initial mating (for review see ref. 4). Within females, SP is thought to activate a specific G protein-coupled receptor (SPR) (5) in a small set of internal sensory neurons of the female reproductive tract (6, 7). Signaling by SP and SPR is essential for the modulation of female behavior as these changes do not occur if the male lacks SP (8, 9) or the female lacks SPR (5).The modulation of female reproductive behavior in response to SP (and its closely related homolog DUP99B) (10, 11) is currently the only known role of SPR. Nonetheless, several lines of evidence have hinted that SPR may have other ligands and possibly also other functions. First, SPR is broadly expressed throughout the central nervous system (5), yet it is required only in reproductive tract sensory neurons for the postmating behavioral switch (6, 7). Second, SPR is also expressed in the central nervous system of males (5), where it is not likely to be exposed to SP. Third, orthologs of SPR are clearly d...

Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to enforce gene silencing, but how transcriptional repression is propagated through mitotic cell divisions remains a key unresolved question. Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic stem cells, here we show that PRC1 can trigger transcriptional repression and Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1), but not variant PRC1, maintains gene silencing through cell division upon reversal of tethering. Propagation of gene repression is sustained by cis-acting histone modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, promoting a sequence-independent feedback mechanism for PcG protein recruitment. Thus, the distinct PRC1 complexes present in vertebrates can differentially regulate epigenetic maintenance of gene silencing, potentially enabling dynamic heritable responses to complex stimuli. Our findings reveal how PcG repression is potentially inherited in vertebrates.