Evidence map›Paper›PMID 33661100›Full record

ArticleeLife2021

HP1 proteins compact DNA into mechanically and positionally stable phase separated domains.

Madeline M Keenen, David Brown, Lucy D Brennan, Roman Renger, Harrison Khoo, Christopher R Carlson, Bo Huang, Stephan W Grill, Geeta J Narlikar, Sy Redding

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed
14.3field-weighted citation impact, top 1% of its field
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

136 citing papers in PubMed, 233 citations in OpenAlex.

  1. Article
  2. Article
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  5. Hp1bp3 loss links chromatin reorganization to metabolic vulnerability in glioma.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  8. Review
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  14. Polymorphic 3D genome architecture mediated by transposable elements.bioRxiv : the preprint server for biology · 2026
    Article
  15. Measuring bridging forces in protein-DNA condensates.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

76 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Madeline M KeenenDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
David BrownDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Lucy D BrennanDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Roman RengerMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Harrison KhooDepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, United States.
Christopher R CarlsonTetrad Graduate Program, University of California, San Francisco, San Francisco, United States.
Bo HuangDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0003-1704-4141
Stephan W GrillMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.ORCID 0000-0002-2290-5826
Geeta J NarlikarDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-1920-0147
Sy ReddingDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0003-3463-7985
University of California, San Francisco · USGerman Center for Neurodegenerative Diseases · DEJohns Hopkins University · USMarine Biological Laboratory · USMax Planck Institute of Molecular Cell Biology and Genetics · DE

Funding

GENETICS OF EUCARYOTIC AND PROCARYOTIC ORGANISMST32GM007810 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHRAFI, KAVEH, NARLIKAR, GEETA J · 1985 to 2020
$15.1M
Measuring the lifetime and mechanical stability of phase-separated heterochromatin domainsR35GM127020 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GEETA J NARLIKAR · 2018 to 2026
$7.3M
Mapping endogenous protein dynamics in living cellsR01GM131641 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Bo Huang · 2019 to 2026
$2.6M
(PQ7) Defining a new mode of RAS signaling in cancer from cytoplasmic protein granulesR01CA231300 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G, HUANG, BO · 2019 to 2023
$2.3M
Structure mapping of molecular complexes by super-resolution microscopyR01GM124334 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, BO · 2018 to 2021
$1.3M
Rapid screening of gene-edited cellsR21GM129652 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, BO · 2018 to 2019
$441k
Multimerized GFP probe for live cell imagingR21EB022798 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, BO · 2016 to 2017
$436k
Dissecting the molecular mechanism of heterochromatin misregulation at the nuclear periphery in cancerF99CA245719 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KEENEN, MADELINE · 2019 to 2020
$82k
NCI NIH HHS F31 CA243360NCI NIH HHS F99 CA245719NCI NIH HHS R01 CA231300NIBIB NIH HHS R21 EB022798NIGMS NIH HHS R01 GM124334NIGMS NIH HHS R01 GM131641NIGMS NIH HHS R21 GM129652NIGMS NIH HHS R35 GM127020NIGMS NIH HHS T32 GM007810
6 · The paper itself

Abstract

In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog's DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale.

Indexed as

Cells, CulturedChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNAHeterochromatinHumansProtein BindingCBX1 protein, humanCBX3 protein, humanCBX5 protein, humanChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNAHeterochromatinbiochemistrychemical biologychromatin organizationheterochromatinhumanmolecular biophysicsphase separationstructural biology

Identifiers

PMID33661100
PMCPMC7932698
OpenAlexW3135396596

What OpenQuestion holds

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LicenceCC BY
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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.