Evidence map›Paper›PMID 42151415›Full record

ArticleNature genetics2026

H3K27me3 spreading organizes canonical PRC1 chromatin architecture to regulate developmental programs.

Brian Krug, Bo Hu, Haifen Chen, Claudia Negrón-Lomas, Xiao Chen, Ahmed El Mouatani, Kristjan H Gretarsson, Adam Ptack, Shriya Deshmukh, Nisha Kabir and 27 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors.

Brian Krug *Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Bo Hu *Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Haifen ChenDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Claudia Negrón-LomasDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Xiao ChenDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Ahmed El MouataniDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Kristjan H GretarssonDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9616-416X
Adam PtackDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Shriya DeshmukhDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0001-9086-3261
Nisha KabirDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Wajih JawharDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Augusto Faria AndradeDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0001-5866-0501
Elias JabbourDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Ashot S HarutyunyanDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-9050-9315
Xinrui WangDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Robert TaylorDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
John J Y LeeThe Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Maud HulswitDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Damien FauryDepartment of Pediatrics, McGill University, The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Caterina RussoDepartment of Pediatrics, McGill University, The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Xinjing XuDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Jiahan YangDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Audrey BaguetteThe Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0001-8011-2341
Nathan A DahlMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Alexander G WeilDepartment of Pediatric Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
Benjamin EllezamDepartment of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
Rola DaliMcGill University Genome Centre, Montreal, Quebec, Canada.
Mathieu BlanchetteSchool of Computer Science, McGill University, Montreal, Quebec, Canada.
Khadija WilsonDepartment of Biochemistry and Biophysics and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Benjamin A GarciaDepartment of Biochemistry and Biophysics and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-3596-4750
Rajesh Kumar SoniProteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-4556-4358
Marco GalloArnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Michael D TaylorArnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Claudia L KleinmanDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-5158-7126
Jacek MajewskiDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-3572-9558
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada. nada.jabado@mcgill.ca.ORCID http://orcid.org/0000-0003-2485-3692
Chao LuDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-0982-8122

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Polycomb repressive complex 2 (PRC2)-mediated histone H3 K27 trimethylation (H3K27me3) recruits canonical PRC1 (cPRC1) to maintain heterochromatin. In early development, Polycomb-regulated genes can display long-range three-dimensional interactions, many of which resolve during lineage differentiation. Here we report that Polycomb-anchored looping is controlled by H3K27me3 spreading and regulates target gene silencing to influence cell fate specification. Using glioma-derived H3 Lys27-to-Met (H3K27M) mutations as tools to restrict H3K27me3 spreading, we show that H3K27me3 confinement concentrates the chromatin pool of cPRC1, resulting in heightened three-dimensional interactions that mirror the chromatin architecture of pluripotency. Conversely, H3K27me3 spread in pluripotent stem cells dilutes local cPRC1 chromatin concentration, weakening Polycomb loop contact frequencies. Disruption of cPRC1 binding or aggregation compromises stringent repression of Polycomb genes and induces differentiation and tumor regression of H3K27M-mutant glioma. These results identify the regulatory principles and disease implications of Polycomb looping and show that histone-modification-guided distribution of reader complexes is an important mechanism for nuclear compartment organization.

Indexed as

ChromatinHistonesPolycomb Repressive Complex 1AnimalsCell Cycle ProteinsCell DifferentiationGliomaHeterochromatinHumansMethylationMiceMutationPluripotent Stem CellsPolycomb-Group ProteinsPolycomb Repressive Complex 2Cell Cycle ProteinsChromatinHeterochromatinHistonesPolycomb-Group ProteinsPolycomb Repressive Complex 1Polycomb Repressive Complex 2PRC1 protein, human

Identifiers

PMID42151415

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.