Evidence map›Paper›PMID 35235780›Full record

ArticleCell reports2022

dCas9 fusion to computer-designed PRC2 inhibitor reveals functional TATA box in distal promoter region.

Shiri Levy, Logeshwaran Somasundaram, Infencia Xavier Raj, Diego Ic-Mex, Ashish Phal, Sven Schmidt, Weng I Ng, Daniel Mar, Justin Decarreau, Nicholas Moss and 10 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Next-generation direct reprogramming.Frontiers in cell and developmental biology · 2024
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. AI-driven designed protein epigenomics.Clinical research in oncology · 2023
    Article
  15. Review
  16. Review
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

20 authors at 3 institutions in 3 countries.

Shiri LevyInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Logeshwaran SomasundaramInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Infencia Xavier RajInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Diego Ic-MexInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Ashish PhalInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, School of Medicine, Seattle, WA 98105, USA.
Sven SchmidtInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Weng I NgInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Daniel MarInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, Seattle, WA 98195, USA.
Justin DecarreauDepartment of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Nicholas MossInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Division of Medical Genetics, Department of Medicine, University of Washington, School of Medicine, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Ammar AlghadeerInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Oral Health Sciences, University of Washington, School of Dentistry, Seattle, WA 98109, USA; Department of Biomedical Dental Sciences, Imam Abdulrahman Bin Faisal University, College of Dentistry, Dammam 31441, Saudi Arabia.
Henrik HonkanenInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Jay SarthyBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Cancer and Blood Disorder Center, Seattle Children's Hospital, Seattle, WA 98105, USA.
Nicholas A VitanzaThe Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Washington, Seattle, WA, USA.
R David HawkinsInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Division of Medical Genetics, Department of Medicine, University of Washington, School of Medicine, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Julie MathieuInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
Yuliang WangInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA 98195, USA.
David BakerDepartment of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Karol BomsztykInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, Seattle, WA 98195, USA.
Hannele Ruohola-BakerInstitute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, School of Medicine, Seattle, WA 98195, USA; Department of Bioengineering, University of Washington, School of Medicine, Seattle, WA 98105, USA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Oral Health Sciences, University of Washington, School of Dentistry, Seattle, WA 98109, USA. Electronic address: hannele@u.washington.edu.
University of Washington · USHoward Hughes Medical Institute · USSeattle Children's Hospital · US

Funding

Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI WARE, CAROL B · 2007 to 2017
$20.6M
PIXUL-FFPE: High throughput platform for chromatin and DNA sample preparation from formalin fixed paraffin embedded (FFPE) tissue samples- supplement application.R42HG010855 · NHGRI · MATCHSTICK TECHNOLOGIES, INC. · PI BOMSZTYK, KAROL · 2019 to 2022
$2.4M
Influence of Pre-Analytical Factors in Globlastoma MGMT Promoter Methylation Biomarker AssayU01CA246503 · NCI · UNIVERSITY OF WASHINGTON · PI BOMSZTYK, KAROL, ROSTOMILY, ROBERT C · 2020 to 2024
$2.0M
MicroRNA Function in Human Embryonic Stem CellsR01GM083867 · NIGMS · UNIVERSITY OF WASHINGTON · PI RUOHOLA-BAKER, HANNELE · 2008 to 2011
$1.5M
Acquisition of Embryonic Stem Cell Metabolic Signature - Minority SupplementR01GM097372 · NIGMS · UNIVERSITY OF WASHINGTON · PI RUOHOLA-BAKER, HANNELE · 2011 to 2014
$1.3M
NCI NIH HHS U01 CA246503NHGRI NIH HHS R42 HG010855NIGMS NIH HHS P01 GM081619NIGMS NIH HHS R01 GM083867NIGMS NIH HHS R01 GM097372
6 · The paper itself

Abstract

Bifurcation of cellular fates, a critical process in development, requires histone 3 lysine 27 methylation (H3K27me3) marks propagated by the polycomb repressive complex 2 (PRC2). However, precise chromatin loci of functional H3K27me3 marks are not yet known. Here, we identify critical PRC2 functional sites at high resolution. We fused a computationally designed protein, EED binder (EB), which competes with EZH2 and thereby inhibits PRC2 function, to dCas9 (EBdCas9) to allow for PRC2 inhibition at a precise locus using gRNA. Targeting EBdCas9 to four different genes (TBX18, p16, CDX2, and GATA3) results in precise H3K27me3 and EZH2 reduction, gene activation, and functional outcomes in the cell cycle (p16) or trophoblast transdifferentiation (CDX2 and GATA3). In the case of TBX18, we identify a PRC2-controlled, functional TATA box >500 bp upstream of the TBX18 transcription start site (TSS) using EBdCas9. Deletion of this TATA box eliminates EBdCas9-dependent TATA binding protein (TBP) recruitment and transcriptional activation. EBdCas9 technology may provide a broadly applicable tool for epigenomic control of gene regulation.

Indexed as

HistonesPolycomb Repressive Complex 2ChromatinComputersTATA BoxChromatinHistonesPolycomb Repressive Complex 2cancerCRISPR-Cas9epigeneticsEZH2H3K27me3PRC2protein designstem cellsTATA boxtrophoblast

Identifiers

PMID35235780
PMCPMC8984963
OpenAlexW4214750966

What Socratic 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 Socratic graph.