Evidence map›Paper›PMID 32603710›Full record

ArticleMolecular cell2020

The Histone Chaperone FACT Induces Cas9 Multi-turnover Behavior and Modifies Genome Manipulation in Human Cells.

Alan S Wang, Leo C Chen, R Alex Wu, Yvonne Hao, David T McSwiggen, Alec B Heckert, Christopher D Richardson, Benjamin G Gowen, Katelynn R Kazane, Jonathan T Vu and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.8field-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

24 citing papers in PubMed, 53 citations in OpenAlex.

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  16. Molecular mechanisms ofBiophysics reports · 2021
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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

15 authors at 5 institutions in 2 countries.

Alan S WangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Leo C ChenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
R Alex WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Yvonne HaoDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
David T McSwiggenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute of Regenerative Medicine Center of Excellence, University of California, Berkeley, Berkeley, CA 94720, USA.
Alec B HeckertDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute of Regenerative Medicine Center of Excellence, University of California, Berkeley, Berkeley, CA 94720, USA.
Christopher D RichardsonDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Benjamin G GowenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Katelynn R KazaneDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Jonathan T VuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Stacia K WymanDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Jiyung J ShinDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Xavier DarzacqDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute of Regenerative Medicine Center of Excellence, University of California, Berkeley, Berkeley, CA 94720, USA.
Johannes C WalterDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Jacob E CornDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Biology, ETH Zürich, 8093 Zürich, Switzerland. Electronic address: jacob.corn@biol.ethz.ch.
Innovative Genomics Institute · USCalifornia Institute for Regenerative Medicine · USHoward Hughes Medical Institute · USETH Zurich · CHUniversity of California, Berkeley · US

Funding

Center for 3D Structure and Physics of the GenomeU54DK107980 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DEKKER, JOB, MIRNY, LEONID A · 2015 to 2019
$14.9M
The Fanconi anemia pathway: role in DNA interstrand cross-link repairR01HL098316 · NHLBI · HARVARD MEDICAL SCHOOL · PI Johannes Walter · 2010 to 2026
$6.3M
Tools For Imaging the Functional Genome in Living Cells and TissuesU01EB021236 · NIBIB · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI DARZACQ, XAVIER, SINGER, ROBERT H · 2015 to 2017
$2.5M
Stem Cell Engineering Training ProgramT32GM098218 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HEALY, KEVIN EDWARD, SCHAFFER, DAVID V · 2011 to 2020
$1.8M
Tools For Imaging the Functional Genome in Living Cells and TissuesU01DA047729 · NIDA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI DARZACQ, XAVIER, SINGER, ROBERT H · 2018 to 2019
$1.7M
Pacific Biosciences PacBio RS Single Molecule Real Time SequencerS10OD018174 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ROKHSAR, DANIEL SOLEYMAN · 2014 to 2014
$600k
Howard Hughes Medical InstituteNHLBI NIH HHS R01 HL098316NIBIB NIH HHS U01 EB021236NIBIB NIH HHS UO1-497 EB021236NIDA NIH HHS U01 DA047729NIDDK NIH HHS U54 DK107980NIGMS NIH HHS T32 GM098218NIH HHS S10 OD018174
6 · The paper itself

Abstract

Cas9 is a prokaryotic RNA-guided DNA endonuclease that binds substrates tightly in vitro but turns over rapidly when used to manipulate genomes in eukaryotic cells. Little is known about the factors responsible for dislodging Cas9 or how they influence genome engineering. Unbiased detection through proximity labeling of transient protein interactions in cell-free Xenopus laevis egg extract identified the dimeric histone chaperone facilitates chromatin transcription (FACT) as an interactor of substrate-bound Cas9. FACT is both necessary and sufficient to displace dCas9, and FACT immunodepletion converts Cas9's activity from multi-turnover to single turnover. In human cells, FACT depletion extends dCas9 residence times, delays genome editing, and alters the balance between indel formation and homology-directed repair. FACT knockdown also increases epigenetic marking by dCas9-based transcriptional effectors with a concomitant enhancement of transcriptional modulation. FACT thus shapes the intrinsic cellular response to Cas9-based genome manipulation most likely by determining Cas9 residence times.

Indexed as

Genome, HumanAnimalsCell LineCRISPR-Associated Protein 9CRISPR-Associated ProteinsDNADNA-Binding ProteinsDNA Breaks, Double-StrandedDNA RepairEpigenesis, GeneticGene EditingGene Knockdown TechniquesHigh Mobility Group ProteinsHumansNucleosomesTranscriptional Elongation FactorsCRISPR-Associated Protein 9CRISPR-Associated ProteinsDNADNA-Binding ProteinsHigh Mobility Group ProteinsNucleosomesSSRP1 protein, humanTranscriptional Elongation FactorsCas9CRISPRCRISPRaCRISPRiFACT complexhistone chaperoneSPT16SSRP1

Identifiers

PMID32603710
PMCPMC7398558
OpenAlexW3037288046

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.