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The SUMO ligase Su(var)2-10 links piRNA-guided target recognition to chromatin silencing

Ninova, Maria and Chen, Yung-Chia Ariel and Godneeva, Baira and Rogers, Alicia K. and Luo, Yicheng and Aravin, Alexei A. and Fejes Tóth, Katalin (2019) The SUMO ligase Su(var)2-10 links piRNA-guided target recognition to chromatin silencing. . (Unpublished)

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Regulation of transcription is the main mechanism responsible for precise control of gene expression. While the majority of transcriptional regulation is mediated by a multitude of DNA-binding transcription factors that bind to regulatory gene regions, an elegant alternative strategy employs small RNA guides, piwi-interacting RNAs (piRNAs) to identify targets of transcriptional repression. Here we show that in Drosophila the small ubiquitin-like protein SUMO and the SUMO E3 ligase Su(var)2-10 are required for piRNA-guided deposition of repressive chromatin marks and transcriptional silencing of piRNA targets. Su(var)2-10 links the piRNA-guided target recognition complex to the silencing effector by binding the piRNA/Piwi complex and inducing SUMO-dependent recruitment of the SetDB1/Wde histone methyltransferase effector. We propose that in Drosophila, the nuclear piRNA pathway has co-opted a conserved mechanism of SUMO-dependent recruitment of the SetDB1/Wde chromatin modifier to confer repression of genomic parasites.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper Information
Ninova, Maria0000-0001-5051-5502
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We thank members of the Fejes Toth and Aravin labs for discussion. We thank Gary Karpen for suggestions and discussion of some of the experiments. We appreciate the help of Kathy Situ, Zsófia Török, Sivani Vempati, Solomiia Khomandiak, and Angel Galvez Merchan with the experiments. We are grateful to Julius Brennecke, Gregory Hannon and the Bloomington Stock Center for providing fly stocks, Julius Brennecke and Giacomo Cavalli for providing antibodies, Andreas Wodarz for the GFP-wde expression vector, and Guntram Suske for the GST-Smt3 (wild type) plasmid. We thank Igor Antoshechkin (Caltech) for help with sequencing and Sergei Manakov for bioinformatic support. This work was supported by grants from the National Institutes of Health (R01 GM097363), the Ministry of Education and Science of Russian Federation (14.W03.31.0007) and by the Packard Fellowship Awards to A.A.A., and the National Institutes of Health (R01GM110217) and Ellison Medical Foundation Awards to K.F.T. AKR was an NSF GRFP fellow. Author contributions: MN, YAC, AAA and KFT designed the experiments. MN, YAC, BG, AR, KFT and YL executed the experiments. MN performed the computational analysis and interpretation of the data. The manuscript was written by MN, YAC, AAA and KFT. Data availability: RNA-seq and H3K9me3 ChIP-seq data from shPiwi and corresponding shW control lines were previously published (LeThomas et al., 2013). All RNA-seq and ChIP-seq data generated in this study is deposited to the Gene Expression Omnibus database: GSE115277. The authors declare no competing interests.
Funding AgencyGrant Number
NIHR01 GM097363
Ministry of Education and Science of the Russian Federation14.W03.31.0007
David and Lucile Packard FoundationUNSPECIFIED
NIHR01 GM110217
Ellison Medical FoundationUNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Record Number:CaltechAUTHORS:20190130-162009709
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Official Citation:The SUMO ligase Su(var)2-10 links piRNA-guided target recognition to chromatin silencing Maria Ninova, Yung-Chia Ariel Chen, Baira Godneeva, Alicia K Rogers, Yicheng Luo, Alexei A Aravin, Katalin Fejes Tóth bioRxiv 533091; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92533
Deposited By: George Porter
Deposited On:31 Jan 2019 23:16
Last Modified:03 Oct 2019 20:45

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