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Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE173237 | GEO | 2021/08/22

REPOSITORIES: GEO

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Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci

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.

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

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

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Panoramix SUMOylation on chromatin connects the piRNA pathway to the cellular heterochromatin machinery.

Project description:Nuclear Argonaute proteins, guided by small RNAs, mediate sequence-specific heterochromatin formation. The molecular principles that link Argonaute-small RNA complexes to cellular heterochromatin effectors on binding to nascent target RNAs are poorly understood. Here, we explain the mechanism by which the PIWI-interacting RNA (piRNA) pathway connects to the heterochromatin machinery in Drosophila. We find that Panoramix, a corepressor required for piRNA-guided heterochromatin formation, is SUMOylated on chromatin in a Piwi-dependent manner. SUMOylation, together with an amphipathic LxxLL motif in Panoramix's intrinsically disordered repressor domain, 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 eliminate the Panoramix-Sov interaction or that prevent SUMOylation of Panoramix uncouple Sov from the piRNA pathway, resulting in viable but sterile flies in which Piwi-targeted transposons are derepressed. Thus, Piwi engages the heterochromatin machinery specifically at transposon loci by coupling recruitment of a corepressor to nascent transcripts with its SUMOylation.

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Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci

Project description:Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci

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

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

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

Project description:Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci [ChIP-seq]

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Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci [CUT&RUN]

Project description:Panoramix SUMOylation at chromatin recruits the heterochromatin machinery to piRNA target loci [CUT&RUN]