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Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci [RNA-seq]

ABSTRACT: Nuclear Argonaute proteins, guided by small RNAs, mediate sequence-specific heterochromatin formation. The molecular principles that link Argonaute–small RNA complexes, once bound to a nascent target RNA, to general heterochromatin effectors are poorly understood. Here, we uncover the mechanistic basis of how the PIWI interacting RNA (piRNA) pathway engages the heterochromatin machinery in Drosophila. Piwi-mediated recruitment of the corepressor complex SFiNX to chromatin leads to SUMOylation of its Panoramix subunit. SUMOylation, together with a hydrophobic LxxLL motif in the intrinsically disordered repressor domain of Panoramix, are necessary and sufficient to recruit Small ovary (Sov), a multi-zinc finger protein essential for general heterochromatin formation and viability. Structure-guided mutations that abrogate the Panoramix-Sov interaction or that prevent Panoramix SUMOylation uncouple Sov from the piRNA pathway, resulting in viable but sterile flies that exhibit de-repression of Piwi-targeted transposons. Thus, coupling the piRNA-guided recruitment of a corepressor to chromatin with its SUMOylation underlies sequence-specific heterochromatin formation.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE173222 | GEO | 2021/08/22

REPOSITORIES: GEO

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Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci [GRO-seq]

Project description:Nuclear Argonaute proteins, guided by small RNAs, mediate sequence-specific heterochromatin formation. The molecular principles that link Argonaute–small RNA complexes, once bound to a nascent target RNA, to general heterochromatin effectors are poorly understood. Here, we uncover the mechanistic basis of how the PIWI interacting RNA (piRNA) pathway engages the heterochromatin machinery in Drosophila. Piwi-mediated recruitment of the corepressor complex SFiNX to chromatin leads to SUMOylation of its Panoramix subunit. SUMOylation, together with a hydrophobic LxxLL motif in the intrinsically disordered repressor domain of Panoramix, are necessary and sufficient to recruit Small ovary (Sov), a multi-zinc finger protein essential for general heterochromatin formation and viability. Structure-guided mutations that abrogate the Panoramix-Sov interaction or that prevent Panoramix SUMOylation uncouple Sov from the piRNA pathway, resulting in viable but sterile flies that exhibit de-repression of Piwi-targeted transposons. Thus, coupling the piRNA-guided recruitment of a corepressor to chromatin with its SUMOylation underlies sequence-specific heterochromatin formation.

2021-08-22 | GSE173236 | GEO

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A nuclear RNA export factor variant licenses piRNA-guided heterochromatin formation

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2019-06-12 | PXD011201 | Pride

The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation

Project description:The PIWI-interacting RNA (piRNA) pathway protects animal genome integrity in part through establishing repressive heterochromatin at transposon loci. Silencing requires piRNA- guided targeting of nuclear PIWI proteins to nascent transposon transcripts, yet the subsequent molecular events are not understood. Here, we identify SFiNX (Silencing Factor interacting Nuclear eXport variant), an interdependent protein complex required for Piwi-mediated co-transcriptional silencing in Drosophila. SFiNX consists of Nxf2-Nxt1, a gonad- specific variant of the heterodimeric mRNA export receptor Nxf1-Nxt1, and the Piwi-associated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon de-repression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits the cellular heterochromatin machinery, while Nxf2 binds the nascent target RNA and licenses co-transcriptional silencing. Our results reveal an unexpected, RNA-export independent role for Nxf2 in nuclear small RNA biology and suggest that NXF-variants, which have largely unknown function in animals, are functionally linked to the genome-transposon conflict.

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Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila

Project description:In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.

2021-01-26 | PXD022105 | Pride

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2021-01-26 | PXD022103 | Pride

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