Su(var)2-10 and the SUMO Pathway Link piRNA-Guided Target Recognition to Chromatin Silencing
Abstract
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.
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.Attached Files
Accepted Version - nihms-1544123.pdf
Submitted - 533091.1.full.pdf
Supplemental Material - 1-s2.0-S109727651930841X-mmc1.pdf
Files
1-s2.0-S109727651930841X-mmc1.pdf
Additional details
Additional titles
- Alternative title
- The SUMO ligase Su(var)2-10 links piRNA-guided target recognition to chromatin silencing
Identifiers
- PMCID
- PMC7007863
- Eprint ID
- 92533
- Resolver ID
- CaltechAUTHORS:20190130-162009709
Related works
- Describes
- 10.1101/533091 (DOI)
Funding
- NIH
- R01 GM097363
- Ministry of Education and Science of the Russian Federation
- 14.W03.31.0007
- David and Lucile Packard Foundation
- NIH
- R01 GM110217
- Ellison Medical Foundation
- NSF Graduate Research Fellowship
Dates
- Created
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2019-01-31Created from EPrint's datestamp field
- Updated
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2023-07-21Created from EPrint's last_modified field