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SUMO ligase Su(var)2-10 controls eu- and heterochromatic gene expression via establishment of H3K9 trimethylation and negative feedback regulation

Ninova, Maria and Godneeva, Baira and Chen, Yung-Chia Ariel and Luo, Yicheng and Prakash, Sharan J. and Jankovics, Ferenc and Erdélyi, Miklós and Fejes Tóth, Katalin and Aravin, Alexei A. (2019) SUMO ligase Su(var)2-10 controls eu- and heterochromatic gene expression via establishment of H3K9 trimethylation and negative feedback regulation. . (Unpublished) http://resolver.caltech.edu/CaltechAUTHORS:20190130-121936593

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Abstract

Сhromatin is critical for genome compaction and gene expression. On a coarse scale, the genome is divided into euchromatin, which harbors the majority of genes and is enriched in active chromatin marks, and heterochromatin, which is gene-poor but repeat-rich. The conserved molecular hallmark of heterochromatin is the H3K9me3 modification, which is associated with gene silencing. We found that in Drosophila deposition of most of the H3K9me3 mark depends on SUMO and the SUMO-ligase Su(var)2-10, which recruits the histone methyltransferase complex SetDB1/Wde. In addition to repressing repeats, H3K9me3 also influences expression of both hetero- and euchromatic host genes. High H3K9me3 levels in heterochromatin are required to suppress spurious non-canonical transcription and ensure proper gene expression. In euchromatin, a set of conserved genes is repressed by Su(var)2-10/SetDB1-induced H3K9 trimethylation ensuring tissue-specific gene expression. Several components of heterochromatin are themselves repressed by this pathway providing a negative feedback mechanism to ensure chromatin homeostasis.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/533232DOIDiscussion Paper
https://www.biorxiv.org/content/10.1101/533232v1.supplementary-materialPublisherSupporting Information
ORCID:
AuthorORCID
Ninova, Maria0000-0001-5051-5502
Additional Information:he 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 are grateful to the Bloomington Stock Center and Julius Brennecke for providing fly stocks. We thank Igor Antoshechkin (Caltech) for help with sequencing. 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.. Data availability: All RNA-seq and ChIP-seq data generated for this study and for the accompanying manuscript (Ninova et al, accompanying manuscript) were deposited into the Gene Expression Omnibus (GEO) database under accession GSE115277. H3K9me3 ChIP-seq data for shSov and respective controls was deposited to GEO under accession GSE125055. Author contributions: MN, AAA and KFT designed the experiments. MN, BG, YL, YAC and SP executed the experiments, FJ and ME generated reagents. MN performed the computational analysis and interpretation of the data. The manuscript was written by MN, AAA and KFT. The authors declare no competing interests.
Funders:
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
Subject Keywords:chromatin, heterochromatin, epigenetics, gene regulation, transcriptional repression, transposons, germline, cell fate maitanance
Record Number:CaltechAUTHORS:20190130-121936593
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190130-121936593
Official Citation:The SUMO ligase Su(var)2-10 controls eu- and heterochromatic gene expression via establishment of H3K9 trimethylation and negative feedback regulation Maria Ninova, Baira Godneeva, Yung-Chia Ariel Chen, Yicheng Luo, Sharan J Prakash, Ferenc Jankovics, Miklós Erdélyi, Katalin Fejes Tóth, Alexei A Aravin bioRxiv 533232; doi: https://doi.org/10.1101/533232
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92523
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:31 Jan 2019 00:14
Last Modified:31 Jan 2019 00:14

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