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Updated: May 31, 2026

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
Published on: May 5, 2023
Tight protein-DNA interactions favor gene silencing
Marion Dubarry1, Isabelle Loïodice, Chunlong L Chen
1Institut Curie, Paris, F-75248 France.
None:
The heterochromatin-like structure formed by the yeast silent information regulator complex (SIR) represses transcription at the silent mating type loci and telomeres. Here, we report that tight protein-DNA complexes induce ectopic recruitment of the SIR complex, promoting gene silencing and changes in subnuclear localization when cis-acting elements are nearby. Importantly, lack of the replication fork-associated helicase Rrm3 enhances this induced gene repression. Additionally, Sir3 and Sir4 are enriched genome-wide at natural replication pause sites, including tRNA genes. Consistently, inserting a tRNA gene promotes SIR-mediated silencing of a nearby gene. These results reveal that replication stress arising from tight DNA-protein interactions favors heterochromatin formation.
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