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Su(var)2-10 and the SUMO Pathway Link 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 Fejes Tóth, Katalin and Aravin, Alexei A. (2020) Su(var)2-10 and the SUMO Pathway Link piRNA-Guided Target Recognition to Chromatin Silencing. Molecular Cell, 77 (3). pp. 556-570. ISSN 1097-2765. PMCID PMC7007863 .

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Regulation of transcription is the main mechanism responsible for precise control of gene expression. Whereas the majority of transcriptional regulation is mediated by 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:Article
Related URLs:
URLURL TypeDescription Paper CentralArticle
Ninova, Maria0000-0001-5051-5502
Rogers, Alicia K.0000-0001-5525-6095
Luo, Yicheng0000-0003-3704-2389
Fejes Tóth, Katalin0000-0001-6558-2636
Aravin, Alexei A.0000-0002-6956-8257
Alternate Title:The SUMO ligase Su(var)2-10 links piRNA-guided target recognition to chromatin silencing
Additional Information:© 2019 Elsevier Inc. Received 13 February 2019, Revised 11 June 2019, Accepted 8 November 2019, Available online 31 December 2019. 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; 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 NIH (R01 GM097363) and 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 NIH (R01GM110217) and the Ellison Medical Foundation Awards to K.F.T. A.K.R. was an NSF GRFP fellow. Author Contributions: M.N., Y.A.C., A.A.A., and K.F.T. designed the experiments. M.N., Y.A.C., B.G., A.R., K.F.T., and Y.L. executed the experiments. M.N. performed the computational analysis and interpretation of the data. The manuscript was written by M.N., Y.A.C., A.A.A., and K.F.T. 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
Subject Keywords:piRNA; Su(var)2-10; SUMO; chromatin; heterochromatin; silencing; transposon
Issue or Number:3
PubMed Central ID:PMC7007863
Record Number:CaltechAUTHORS:20190130-162009709
Persistent URL:
Official Citation:Maria Ninova, Yung-Chia Ariel Chen, Baira Godneeva, Alicia K. Rogers, Yicheng Luo, Katalin Fejes Tóth, Alexei A. Aravin, Su(var)2-10 and the SUMO Pathway Link piRNA-Guided Target Recognition to Chromatin Silencing, Molecular Cell, Volume 77, Issue 3, 2020, Pages 556-570.e6, ISSN 1097-2765, (
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:16 Nov 2020 22:38

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