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


Authors: Andreev, V. I.; Yu, C.; Wang, J.; Schnabl, J.; Tirian, L.; Gehre, M.; Handler, D.; Duchek, P.; Novatchkova, M.; Baumgartner, L.; Meixner, K.; Sienski, G.; Patel, D. J.; Brennecke, J.
Article Title: Panoramix SUMOylation on chromatin connects the piRNA pathway to the cellular heterochromatin machinery
Abstract: 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. © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
Journal Title: Nature Structural and Molecular Biology
Volume: 29
Issue: 2
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2022-02-01
Start Page: 130
End Page: 142
Language: English
DOI: 10.1038/s41594-022-00721-x
PUBMED: 35173350
PROVIDER: scopus
PMCID: PMC11749891
DOI/URL:
Notes: Article -- Export Date: 1 March 2022 -- Source: Scopus
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  1. Dinshaw J Patel
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  2. Juncheng Wang
    12 Wang