Evidence map›Paper›PMID 42400910›Full record

ArticleCell reports2026

Physical interactions within the SIR heterochromatin complex potentiate inter-subunit communication and gene repression.

Jenna Kotz, E J Martz, Maya Nelson, Nicole Savoie, Lauren Schmitt, Jordan States, Nathan Holton, Danielle Guillen, Vignesh Kasinath, Kirk Hansen and 1 more

Abstract read
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jenna KotzDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA; Structural Biology, Biochemistry, and Biophysics Program, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
E J MartzDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA; Structural Biology, Biochemistry, and Biophysics Program, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
Maya NelsonDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
Nicole SavoieDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
Lauren SchmittDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA; Structural Biology, Biochemistry, and Biophysics Program, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
Jordan StatesDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
Nathan HoltonDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
Danielle GuillenDepartment of Biochemistry, University of Colorado - Boulder, Boulder, CO, USA.
Vignesh KasinathDepartment of Biochemistry, University of Colorado - Boulder, Boulder, CO, USA.
Kirk HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA; Structural Biology, Biochemistry, and Biophysics Program, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA.
Aaron M JohnsonDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA; Structural Biology, Biochemistry, and Biophysics Program, University of Colorado, Denver - Anschutz Medical Campus, Aurora, CO, USA. Electronic address: aaron.m.johnson@cuanschutz.edu.

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Predoctoral Training Molecular BiophysicsT32GM065103 · NIGMS · UNIVERSITY OF COLORADO AT BOULDER · PI FALKE, JOSEPH J · 2002 to 2021
$4.3M
Interdisciplinary Predoctoral Training in Molecular BiophysicsT32GM145437 · NIGMS · UNIVERSITY OF COLORADO · PI JOSEPH J FALKE · 2022 to 2026
$2.5M
Mechanisms of heterochromatin targeting and epigenetic genome regulationR35GM144358 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Aaron M. Johnson · 2022 to 2026
$2.1M
Structure and Mechanism of Epigenetic Gene SilencingR35GM155426 · NIGMS · UNIVERSITY OF COLORADO · PI Vignesh Kasinath · 2024 to 2026
$1.2M
Uncovering the Role of Synaptonemal Complex in Meiotic Recombination by Cryo-electron TomographyR00GM132544 · NIGMS · UNIVERSITY OF COLORADO · PI KASINATH, VIGNESH · 2021 to 2023
$747k
NCI NIH HHS P30 CA046934NIGMS NIH HHS R00 GM132544NIGMS NIH HHS R35 GM144358NIGMS NIH HHS R35 GM155426NIGMS NIH HHS T32 GM065103NIGMS NIH HHS T32 GM145437
6 · The paper itself

Abstract

The Saccharomyces cerevisiae silent information regulator (SIR) complex performs all core heterochromatin functions. It first drives histone deacetylation in an iterative, spreading manner, then stably incorporates with nucleosomes to compact and epigenetically repress the chromatin. How this switch between dynamic spreading and stable compaction occurs has remained poorly understood, partly due to limited structural data on the intact complex. Using crosslinking mass spectrometry, we identified an uncharacterized inter-subunit interaction connecting these two states: the Sir2 deacetylase interacts with the scaffolding subunit Sir4 through its coiled-coil domain, which also contacts the Sir3 compaction subunit. This interaction hub contains conserved Sir2 residues that can adopt multiple conformations, including orientation toward the active site, alongside co-evolved residues that enable species-specific Sir4 interactions. Mutations disrupting this hub disrupt heterochromatic repression in vivo and affect the deacetylation activity, directly linking catalysis to compaction. Our findings reveal how a multifunctional complex stages a stepwise transition to achieve epigenetic gene repression.

Indexed as

Gene Expression Regulation, FungalHeterochromatinSaccharomyces cerevisiaeSilent Information Regulator Proteins, Saccharomyces cerevisiaeSirtuin 2AcetylationProtein BindingProtein SubunitsSaccharomyces cerevisiae ProteinsHeterochromatinProtein SubunitsSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSIR2 protein, S cerevisiaeSIR3 protein, S cerevisiaeSIR4 protein, S cerevisiaeSirtuin 2CP: molecular biologycrosslinking mass spectrometryepigeneticsHDACheterochromatinsirtuinyeast

Identifiers

PMID42400910
PMCPMC13531843

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.