Evidence map›Paper›PMID 33208532›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin.

Rachel Leicher, Eva J Ge, Xingcheng Lin, Matthew J Reynolds, Wenjun Xie, Thomas Walz, Bin Zhang, Tom W Muir, Shixin Liu

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

33 citing papers in PubMed, 65 citations in OpenAlex.

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  11. Two-way feedback between chromatin compaction and histone modification state explainsProceedings of the National Academy of Sciences of the United States of America · 2024
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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

9 authors at 4 institutions in 1 country.

Rachel LeicherLaboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY 10065.ORCID 0000-0002-3187-1234
Eva J GeDepartment of Chemistry, Princeton University, Princeton, NJ 08544.
Xingcheng LinDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-9378-6174
Matthew J ReynoldsLaboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, NY 10065.ORCID 0000-0002-2501-9280
Wenjun XieDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-3982-9305
Thomas WalzLaboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY 10065.ORCID 0000-0003-2606-2835
Bin ZhangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; binz@mit.edu shixinliu@rockefeller.edu.ORCID 0000-0002-3685-7503
Tom W MuirDepartment of Chemistry, Princeton University, Princeton, NJ 08544.ORCID 0000-0001-9635-0344
Shixin LiuLaboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY 10065; binz@mit.edu shixinliu@rockefeller.edu.ORCID 0000-0003-4238-7066
Massachusetts Institute of Technology · USRockefeller University · USPrinceton University · USTri-Institutional PhD Program in Chemical Biology · US

Funding

Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI LEWIS, PETER W · 2015 to 2024
$17.6M
Probing and Perturbing Transcriptional Condensates with Multiscale Modeling and Deep LearningR35GM133580 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Bin Zhang · 2019 to 2026
$3.1M
Probing Symmetry Breaking in Epigenetic Inheritance: From Single Molecules to Systems BiologyDP2HG010510 · NHGRI · ROCKEFELLER UNIVERSITY · PI LIU, SHIXIN · 2018 to 2018
$2.5M
NCI NIH HHS P01 CA196539NHGRI NIH HHS DP2 HG010510NIGMS NIH HHS R35 GM133580
6 · The paper itself

Abstract

Polycomb repressive complex 2 (PRC2) installs and spreads repressive histone methylation marks on eukaryotic chromosomes. Because of the key roles that PRC2 plays in development and disease, how this epigenetic machinery interacts with DNA and nucleosomes is of major interest. Nonetheless, the mechanism by which PRC2 engages with native-like chromatin remains incompletely understood. In this work, we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the behavior of PRC2 on polynucleosome arrays. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides reproducing known binding modes in which PRC2 interacts with bare DNA, mononucleosomes, and adjacent nucleosome pairs, our data also provide direct evidence that PRC2 can bridge pairs of distal nucleosomes. In particular, the "1-3" bridging mode, in which PRC2 engages two nucleosomes separated by one spacer nucleosome, is a preferred low-energy configuration. Moreover, we show that the distribution and stability of different PRC2-chromatin interaction modes are modulated by accessory subunits, oncogenic histone mutations, and the methylation state of chromatin. Overall, these findings have implications for the mechanism by which PRC2 spreads histone modifications and compacts chromatin. The experimental and computational platforms developed here provide a framework for understanding the molecular basis of epigenetic maintenance mediated by Polycomb-group proteins.

Indexed as

Models, MolecularChromatinEpigenesis, GeneticHeterochromatinHistonesHumansMethylationModels, BiologicalMolecular Dynamics SimulationMutationNucleosomesPolycomb Repressive Complex 2Protein BindingProtein ConformationSingle Molecule ImagingSpectrum AnalysisChromatinHeterochromatinHistonesNucleosomesPolycomb Repressive Complex 2epigeneticsheterochromatinmolecular dynamics simulationPolycomb-group proteinsingle-molecule force spectroscopy

Identifiers

PMID33208532
PMCPMC7720148
OpenAlexW3104615387

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.