Evidence map›Paper›PMID 41785860›Full record

ArticleMolecular cell2026

Self-clustering of three CBX2 molecules drives PRC2 to promote facultative heterochromatinization of Polycomb target genes.

Steven Ingersoll, Abby Trouth, J Carlos Angel, Xinlong Luo, Axel Espinoza, Joey Wen, Chengjie Zhu, Joseph Tucker, Kalkidan Astatike, Christopher J Phiel and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Steven IngersollDepartment of Chemistry, University of Colorado Denver, Denver, CO 80217, USA; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Abby TrouthDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
J Carlos AngelDepartment of Biomedical Informatics, Columbia University, New York, NY 10032, USA; New York Genome Center, New York, NY 10013, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY 10032, USA.
Xinlong LuoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Axel EspinozaDepartment of Integrative Biology, University of Colorado Denver, Denver, CO 80217, USA.
Joey WenDepartment of Chemistry, University of Colorado Denver, Denver, CO 80217, USA.
Chengjie ZhuDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28262, USA.
Joseph TuckerDepartment of Integrative Biology, University of Colorado Denver, Denver, CO 80217, USA.
Kalkidan AstatikeDepartment of Chemistry, University of Colorado Denver, Denver, CO 80217, USA.
Christopher J PhielDepartment of Integrative Biology, University of Colorado Denver, Denver, CO 80217, USA.
Hatim SabaawyDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Tatiana G KutateladzeDepartment of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Tao P WuDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Tingting YaoDepartment of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
Chao LuDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Srinivas RamachandranDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA; RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: srinivas.ramachandran@cuanschutz.edu.
Xiaojun RenDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28262, USA; Department of Chemistry, University of Colorado Denver, Denver, CO 80217, USA; Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC 28262, USA. Electronic address: xren2@charlotte.edu.

Funding

Maintenance of cellular memory through replicationR35GM133434 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI RAMACHANDRAN, SRINIVAS · 2019 to 2023
$2.0M
Machine-Learning Aided Design of Avidity-Based Biosensors of Ubiquitin SignalingR01CA283904 · NCI · COLORADO STATE UNIVERSITY · PI Robert Cohen, Christopher Davis Snow · 2024 to 2026
$1.3M
Spatial Organization of Epigenetic Complexes and ChromatinR01GM135286 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI PHIEL, CHRISTOPHER J · 2019 to 2022
$1.3M
Maintenance of cellular memory during replicationR35GM156411 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Srinivas Ramachandran · 2025 to 2026
$855k
Understanding MORF-mediated hematological gene regulatory mechanismsR01GM157928 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI TATIANA G KUTATELADZE · 2025 to 2026
$775k
NCI NIH HHS R01 CA283904NIGMS NIH HHS R01 GM135286NIGMS NIH HHS R01 GM157928NIGMS NIH HHS R35 GM133434NIGMS NIH HHS R35 GM156411
6 · The paper itself

Abstract

Phase separation is increasingly recognized in facultative heterochromatinization of Polycomb target genes; however, the mechanisms underlying this process remain obscure. Using single-molecule imaging and tracking, we show that individual condensates in mouse embryonic stem cells (mESCs) contain approximately 3 CBX2 molecules and numerous Polycomb repressive complex (PRC)1 and PRC2 subunits and indicate that the composition and dynamics of condensates are developmentally regulated. We reveal that CBX2 clusters PRC2 and controls the spatial distribution of both PRC2 and H3K27me3. Using genomic approaches, we demonstrate that CBX2 binds to condensate initiation sites, which are enriched for PRC2 nucleation sites. CBX2 deletion causes PRC2 and H3K27me3 to redistribute from their regular targets. By developing a separation-of-function variant, we determine that CBX2 relies on its self-clustering ability to function. These findings collectively support a phase-separation model driven by nucleation and bridging, in which low-abundance proteins self-cluster to initiate condensate assembly, a process tightly coupled to function.

Indexed as

HeterochromatinMouse Embryonic Stem CellsPolycomb Repressive Complex 2AnimalsHistonesMicePhase SeparationPolycomb-Group ProteinsPolycomb Repressive Complex 1Single Molecule ImagingCbx2 protein, mouseHeterochromatinHistonesPolycomb-Group ProteinsPolycomb Repressive Complex 1Polycomb Repressive Complex 2bridging-induced phase separationCBX2chromatinH3K27me3nucleationPcGphase separationPolycombpolymer-polymer phase separationsingle-molecule imaging

Identifiers

PMID41785860
PMCPMC12981346

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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.