Evidence map›Paper›PMID 27130520›Full record

ArticleeLife2016

Nucleosome breathing and remodeling constrain CRISPR-Cas9 function.

R Stefan Isaac, Fuguo Jiang, Jennifer A Doudna, Wendell A Lim, Geeta J Narlikar, Ricardo Almeida

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 1 pooled it
15.3field-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

141 citing papers in PubMed, 1 synthesis or guideline pooled it, 254 citations in OpenAlex.

  1. Pooled it
  2. 3D Genome Engineering Using CRISPR/dCas Systems.International journal of molecular sciences · 2026
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81 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

6 authors at 4 institutions in 1 country.

R Stefan IsaacDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Fuguo JiangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Jennifer A DoudnaCalifornia Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States.
Wendell A LimDepartment of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Geeta J NarlikarDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Ricardo AlmeidaCenter for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, United States.
QB3 · USUniversity of California, San Francisco · USHoward Hughes Medical Institute · USUniversity of California, Berkeley · US

Funding

Mechanistic Analysis of Chromatin RemodelingR01GM073767 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NARLIKAR, GEETA J · 2005 to 2018
$4.7M
Harnessing CRISPR for Targeted and Inducible Epigenomic ReprogrammingR01DA036858 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A, QI, LEI STANLEY · 2013 to 2017
$2.9M
NIDA NIH HHS R01 DA036858NIGMS NIH HHS R01 GM073767
6 · The paper itself

Abstract

The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo.

Indexed as

CRISPR-Cas SystemsRecombination, GeneticAnimalsBacterial ProteinsCRISPR-Associated Protein 9DNAEndonucleasesGene EditingNucleosomesProtein BindingXenopusBacterial ProteinsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9DNAEndonucleasesNucleosomesATP-dependent chromatin remodelingbiochemistrychromatinchromosomesCRISPRCRISPR-Cas9genesnonenucleosome

Identifiers

PMID27130520
PMCPMC4880442
OpenAlexW2342818826

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.