Evidence map›Paper›PMID 28636604›Full record

ArticleNature2017

Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.

Adam G Larson, Daniel Elnatan, Madeline M Keenen, Michael J Trnka, Jonathan B Johnston, Alma L Burlingame, David A Agard, Sy Redding, Geeta J Narlikar

Abstract read
In one paragraph

Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,023 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,023citing papers in PubMed, 1 pooled it
71.1field-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

1,023 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,774 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  13. Transcription and Three-Dimensional Genome Organization: Cause, Consequence, or Coordination?BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  14. Review
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  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Adam G LarsonDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
Daniel ElnatanDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
Madeline M KeenenDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
Michael J TrnkaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94158, USA.
Jonathan B JohnstonDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94158, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94158, USA.
David A AgardDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
Sy ReddingDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
Geeta J NarlikarDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
University of California, San Francisco · US

Funding

Bio-Organic Biomedical Mass Spectromy ResourceP41GM103481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURLINGAME, ALMA L · 2012 to 2015
$6.4M
Structure & Mechanism: microtubule nucleation, centrosomes, phage cytoskeletonR35GM118099 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGARD, DAVID A. · 2016 to 2022
$3.6M
Mechanistic dissection of HP1 mediated heterochromatinR01GM108455 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NARLIKAR, GEETA J · 2014 to 2017
$1.7M
Purchase of Q-Exactive Mass SpectrometerS10OD016229 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURLINGAME, ALMA L · 2013 to 2013
$507k
NIGMS NIH HHS P41 GM103481NIGMS NIH HHS R01 GM108455NIGMS NIH HHS R35 GM118099NIH HHS S10 OD016229
6 · The paper itself

Abstract

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context.

Indexed as

AnimalsChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNAGene SilencingHeterochromatinHumansLigandsMiceNIH 3T3 CellsNucleosomesPhosphorylationSolubilityTranscription Factor TFIIBCBX5 protein, humanChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNAHeterochromatinLigandsNucleosomesTranscription Factor TFIIB

Identifiers

PMID28636604
PMCPMC5606208
OpenAlexW2722642526

What OpenQuestion holds

Textmetadata
LicenceTDM
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.