Molecular Cell
Volume 77, Issue 3, 6 February 2020, Pages 571-585.e4
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Article
The SUMO Ligase Su(var)2-10 Controls Hetero- and Euchromatic Gene Expression via Establishing H3K9 Trimethylation and Negative Feedback Regulation

https://doi.org/10.1016/j.molcel.2019.09.033Get rights and content
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Highlights

  • Heterochromatic gene expression requires H3K9me3 to suppress spurious transcription

  • Deposition of H3K9me3 via Su(var)2-10 ensures tissue-specific gene expression

  • Negative feedback regulation controls expression of several heterochromatin proteins

Summary

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 influences expression of both hetero- and euchromatic host genes. High H3K9me3 levels in heterochromatin are required to suppress spurious 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.

Keywords

chromatin
heterochromatin
epigenetics
gene regulation
transcriptional repression
transposons
germline
cell fate maintenance
SUMO
H3K9me3

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