PT  - JOURNAL ARTICLE
AU  - Maria Ninova
AU  - Baira Godneeva
AU  - Yung-Chia Ariel Chen
AU  - Yicheng Luo
AU  - Sharan J. Prakash
AU  - Ferenc Jankovics
AU  - Miklós Erdélyi
AU  - Katalin Fejes Tóth
AU  - Alexei A. Aravin
TI  - The SUMO ligase Su(var)2-10 controls eu- and heterochromatic gene expression via establishment of H3K9 trimethylation and negative feedback regulation
AID  - 10.1101/533232
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 533232
4099  - http://biorxiv.org/content/early/2019/01/29/533232.short
4100  - http://biorxiv.org/content/early/2019/01/29/533232.full
AB  - Chromatin 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.Highlights- Proper expression of host genes residing in heterochromatin requires Su(var)2-10-dependent installation of the H3K9me3 mark to suppress spurious non-canonical transcription.- A set of euchromatic host genes is repressed by transposon-independent installation of H3K9me3 in a process that depends on Su(var)2-10 and SUMO.- Installation of H3K9me3 via Su(var)2-10 ensures tissue-specific gene expression.- H3K9me3-dependent silencing of genes encoding proteins involved in heterochromatin formation provides negative feedback regulation to maintain heterochromatin homeostasis.