# Blocking heterochromatin spreading constrains cohesin binding at a yeast heterochromatic locus

**Authors:** Paul M. Kraycer, Marc R. Gartenberg

PMC · DOI: 10.1371/journal.pone.0345412 · PLOS One · 2026-03-24

## TL;DR

This study shows that limiting the spread of heterochromatin at a yeast locus also limits cohesin binding in that region.

## Contribution

The paper demonstrates a direct link between heterochromatin spreading and cohesin domain size at the HMR locus in yeast.

## Key findings

- Truncating heterochromatin at HMR reduced the footprint of Sir3 and Smc3.
- Cohesin binding domain size correlates with the size of the heterochromatin domain.
- Artificial barriers built from bacterial DNA binding proteins effectively limited heterochromatin spreading.

## Abstract

Cohesin mediates central features of chromosome architecture. The protein complex governs sister chromatid cohesion and organizes genomes into loops and domains. In budding yeast, cohesin accumulates at discrete sites on chromosome arms, as well as at domains of heterochromatin. The molecular basis for the distribution at these sites is not yet resolved, although the heterochromatin protein Sir2 has been implicated. If cohesin were to bind a recurring feature of heterochromatin, then size of the cohesin domain would match the size of the heterochromatin domain. To test this hypothesis, the span of heterochromatin at the HMR silent mating-type locus was truncated with artificial barrier elements built from bacterial DNA binding proteins. We found that the most effective barrier reduced the footprint of Sir3 and Smc3, representative components of yeast heterochromatin and cohesin. These results show that reducing the span of heterochromatin at HMR constrains the size of the cohesin bound domain.

## Linked entities

- **Proteins:** SIRT2 (sirtuin 2), SIR3 (chromatin-silencing protein SIR3), SMC3 (structural maintenance of chromosomes 3)

## Full-text entities

- **Genes:** HIS3 (imidazoleglycerol-phosphate dehydratase HIS3) [NCBI Gene 854377] {aka HIS10, HIS8}, SIR3 (chromatin-silencing protein SIR3) [NCBI Gene 851163] {aka CMT1, MAR2, STE8}, STAG2 (STAG2 cohesin complex component) [NCBI Gene 10735] {aka HPE13, MKMS, NEDXCF, SA-2, SA2, SCC3B}, SWI6 (transcriptional regulator SWI6) [NCBI Gene 850879] {aka PSL8, SDS11}, SIR4 (chromatin-silencing protein SIR4) [NCBI Gene 851813] {aka ASD1, STE9, UTH2}, SMC3 (cohesin subunit SMC3) [NCBI Gene 853371], URA3 (orotidine-5'-phosphate decarboxylase) [NCBI Gene 856692], SCC2 (cohesin-loading factor complex subunit SCC2) [NCBI Gene 851761], ADE2 (phosphoribosylaminoimidazole carboxylase ADE2) [NCBI Gene 854295], HHT2 (histone H3) [NCBI Gene 855700], MCD1 (kleisin alpha) [NCBI Gene 851561] {aka PDS3, RHC21, SCC1}, SIR1 (Sir1p) [NCBI Gene 853976], PDS5 (sister chromatid cohesion factor PDS5) [NCBI Gene 855099], ACT1 (actin) [NCBI Gene 850504] {aka ABY1, END7}, SMC1 (cohesin subunit SMC1) [NCBI Gene 850540] {aka CHL10}, IRR1 (cohesin subunit IRR1) [NCBI Gene 854786] {aka SCC3}
- **Diseases:** Ewing's sarcoma (MESH:D012512), melanoma (MESH:D008545), glioblastoma (MESH:D005909), cancers (MESH:D009369), developmental diseases (MESH:D001848)
- **Chemicals:** TE (MESH:D013691), formaldehyde (MESH:D005557), sodium deoxycholate (MESH:D003840), 3-aminotriazole (-), NAD (MESH:D009243), TBS (MESH:D013725), Nonidet P-40 (MESH:C010615), EtOH (MESH:D000431), Triton X-100 (MESH:D017830), PBS (MESH:D007854), nocodazole (MESH:D015739), Chelex (MESH:C006960), glycogen (MESH:D006003), leucine (MESH:D007930), KCl (MESH:D011189), 5-fluoro-orotic acid (MESH:C001242), SDS (MESH:D012967), histidine (MESH:D006639), KOH (MESH:C029943), glycine (MESH:D005998), H2O (MESH:D014867), LiCl (MESH:D018021), EDTA (MESH:D004492), SC (MESH:D012538), HEPES (MESH:D006531), NaCl (MESH:D012965)
- **Species:** Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Schizosaccharomyces pombe (fission yeast, species) [taxon 4896]
- **Cell lines:** HMR-I — Mus musculus (Mouse), Hybridoma (CVCL_KR43), MRG7972.0 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_T320), PMK126 — Macaca mulatta (Rhesus macaque), Finite cell line (CVCL_4275), HML — Homo sapiens (Human), Down syndrome, Cancer cell line (CVCL_RL96), MRG7621 — Gorilla gorilla gorilla (Western lowland gorilla), Finite cell line (CVCL_A1AK)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13012450/full.md

## References

56 references — full list in the complete paper: https://tomesphere.com/paper/PMC13012450/full.md

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Source: https://tomesphere.com/paper/PMC13012450