Sir3 mediates long-range chromosome interactions in budding yeast
- Myriam Ruault1,5,
- Vittore F. Scolari1,2,5,
- Luciana Lazar-Stefanita2,3,6,
- Antoine Hocher1,7,
- Isabelle Loïodice1,
- Romain Koszul2,4 and
- Angela Taddei1,4
- 1Institut Curie, PSL University, Sorbonne Université, CNRS, Nuclear Dynamics, 75005 Paris, France;
- 2Institut Pasteur, Unité Régulation Spatiale des Génomes, CNRS, UMR 3525, C3BI USR 3756, F-75015 Paris, France;
- 3Sorbonne Université, collège Doctoral, F-75005 Paris, France;
- 4Cogitamus Laboratory, F-75005 Paris, France
-
↵5 These authors contributed equally to this work.
Abstract
Physical contacts between distant loci contribute to regulate genome function. However, the molecular mechanisms responsible for settling and maintaining such interactions remain poorly understood. Here, we investigate the well-conserved interactions between heterochromatin loci. In budding yeast, the 32 telomeres cluster in 3–5 foci in exponentially growing cells. This clustering is functionally linked to the formation of heterochromatin in subtelomeric regions through the recruitment of the silencing SIR complex composed of Sir2/3/4. Combining microscopy and Hi-C on strains expressing different alleles of SIR3, we show that the binding of Sir3 directly promotes long-range contacts between distant regions, including the rDNA, telomeres, and internal Sir3-bound sites. Furthermore, we unveil a new property of Sir3 in promoting rDNA compaction. Finally, using a synthetic approach, we demonstrate that Sir3 can bond loci belonging to different chromosomes together, when targeted to these loci, independently of its interaction with its known partners (Rap1, Sir4), Sir2 activity, or chromosome context. Altogether, these data suggest that Sir3 acts as a molecular bridge that stabilizes long-range interactions.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.267872.120.
- Received June 29, 2020.
- Accepted December 30, 2020.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
