Evidence map›Paper›PMID 23485968›Full record

ArticleNature2013

A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly.

Daniele Canzio, Maofu Liao, Nariman Naber, Edward Pate, Adam Larson, Shenping Wu, Diana B Marina, Jennifer F Garcia, Hiten D Madhani, Roger Cooke and 3 more

Abstract read
In one paragraph

Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing 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

101 citing papers in PubMed.

  1. Review
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  16. Review
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41 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

13 authors.

Daniele CanzioDepartment of Biochemistry and Biophysics, University of California San Francisco, California 94158, USA.
Maofu Liao
Nariman Naber
Edward Pate
Adam Larson
Shenping Wu
Diana B Marina
Jennifer F Garcia
Hiten D Madhani
Roger Cooke
Peter Schuck
Yifan Cheng
Geeta J Narlikar

Funding

Mechanisms of Gene SilencingR01GM071801 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Hiten D Madhani · 2005 to 2026
$7.1M
Mechanisms Controlling the Super-Relaxed StateR01AR062279 · NIAMS · WASHINGTON STATE UNIVERSITY · PI KOSTYUKOVA, ALLA S. · 2012 to 2016
$2.4M
Biophysical Characterization Of MacromoleculesZIAEB000008 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI SCHUCK, PETER · 2009 to 2019
$1.7M
Molecular dynamics studies of muscle proteinsR01AR053720 · NIAMS · WASHINGTON STATE UNIVERSITY · PI PATE, EDWARD F · 2007 to 2010
$1.1M
Intramural NIH HHSNIAMS NIH HHS AR053720NIAMS NIH HHS R01 AR053720NIAMS NIH HHS R01 AR062279NIGMS NIH HHS R01 GM071801NIGMS NIH HHS R01GM071801
6 · The paper itself

Abstract

A hallmark of histone H3 lysine 9 (H3K9)-methylated heterochromatin, conserved from the fission yeast Schizosaccharomyces pombe to humans, is its ability to spread to adjacent genomic regions. Central to heterochromatin spread is heterochromatin protein 1 (HP1), which recognizes H3K9-methylated chromatin, oligomerizes and forms a versatile platform that participates in diverse nuclear functions, ranging from gene silencing to chromosome segregation. How HP1 proteins assemble on methylated nucleosomal templates and how the HP1-nucleosome complex achieves functional versatility remain poorly understood. Here we show that binding of the key S. pombe HP1 protein, Swi6, to methylated nucleosomes drives a switch from an auto-inhibited state to a spreading-competent state. In the auto-inhibited state, a histone-mimic sequence in one Swi6 monomer blocks methyl-mark recognition by the chromodomain of another monomer. Auto-inhibition is relieved by recognition of two template features, the H3K9 methyl mark and nucleosomal DNA. Cryo-electron-microscopy-based reconstruction of the Swi6-nucleosome complex provides the overall architecture of the spreading-competent state in which two unbound chromodomain sticky ends appear exposed. Disruption of the switch between the auto-inhibited and spreading-competent states disrupts heterochromatin assembly and gene silencing in vivo. These findings are reminiscent of other conditionally activated polymerization processes, such as actin nucleation, and open up a new class of regulatory mechanisms that operate on chromatin in vivo.

Indexed as

Chromatin Assembly and DisassemblyAmino Acid SequenceAnimalsChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneCryoelectron MicroscopyGene SilencingHeterochromatinHistonesMethylationModels, MolecularMolecular Sequence DataNucleosomesProtein Structure, TertiarySchizosaccharomycesSchizosaccharomyces pombe ProteinsChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneHeterochromatinHistonesNucleosomesSchizosaccharomyces pombe ProteinsSwi6 protein, S pombe

Identifiers

PMID23485968
PMCPMC3907283

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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.