Evidence map›Paper›PMID 34354266›Full record

ArticleNature methods2021

Augmenting and directing long-range CRISPR-mediated activation in human cells.

Y Esther Tak, Joy E Horng, Nicholas T Perry, Hayley T Schultz, Sowmya Iyer, Qiuming Yao, Luli S Zou, Martin J Aryee, Luca Pinello, J Keith Joung

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature methods, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. KAS-CUT&Tag for direct mapping of transcription bubbles.bioRxiv : the preprint server for biology · 2026
    Article
  3. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
  4. Article
  5. Regulation Ratio: A Singular Multi-Omic Measurement of Gene Regulatory Mechanisms.Computational and structural biotechnology journal · 2026
    Article
  6. Article
  7. Article
  8. HyperCas12a enables multiplexed CRISPRi screens.bioRxiv : the preprint server for biology · 2025
    Article
  9. International journal of molecular sciences · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Article
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  16. Article
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  18. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Y Esther TakMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
Joy E Horng *Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
Nicholas T Perry *Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.ORCID http://orcid.org/0000-0002-1702-4178
Hayley T SchultzMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
Sowmya IyerMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
Qiuming YaoMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
Luli S ZouCell Circuits and Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Martin J AryeeMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.ORCID http://orcid.org/0000-0002-6848-1344
Luca PinelloMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.
J Keith JoungMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA. jjoung@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-5630-5645
Broad Institute · USMassachusetts General Hospital · USHarvard University · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Evolution, Optimization, and Application of Genome Editing TechnologiesR35GM118158 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2016 to 2023
$4.7M
Functional Effects of Ovarian Cancer Risk VariantsR01CA211707 · NCI · CEDARS-SINAI MEDICAL CENTER · PI FREEDMAN, MATTHEW L, GAYTHER, SIMON ANDREW · 2017 to 2021
$3.3M
Identifying causal variants and genes underlying breast cancer risk lociR01CA204954 · NCI · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L · 2016 to 2020
$3.0M
Multiscale exploration of the functional non-coding genomeR35HG010717 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI PINELLO, LUCA · 2019 to 2023
$2.6M
Common biology underlying pleiotropic breast, prostate and ovarian cancer risk lociR01CA259058 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MATTHEW L FREEDMAN, Simon Andrew Gayther · 2022 to 2026
$2.5M
Discovering disease-causal variants by linking genetic and epigenetic variationR00HG008399 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI PINELLO, LUCA · 2017 to 2019
$747k
NCI NIH HHS R01 CA204954NCI NIH HHS R01 CA211707NCI NIH HHS R01 CA259058NHGRI NIH HHS R00 HG008399NHGRI NIH HHS R35 HG010717NHGRI NIH HHS RM1 HG009490NIGMS NIH HHS R35 GM118158
6 · The paper itself

Abstract

Epigenetic editing is an emerging technology that uses artificial transcription factors (aTFs) to regulate expression of a target gene. Although human genes can be robustly upregulated by targeting aTFs to promoters, the activation induced by directing aTFs to distal transcriptional enhancers is substantially less robust and consistent. Here we show that long-range activation using CRISPR-based aTFs in human cells can be made more efficient and reliable by concurrently targeting an aTF to the target gene promoter. We used this strategy to direct target gene choice for enhancers capable of regulating more than one promoter and to achieve allele-selective activation of human genes by targeting aTFs to single-nucleotide polymorphisms embedded in distally located sequences. Our results broaden the potential applications of the epigenetic editing toolbox for research and therapeutics.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsPromoter Regions, GeneticAllelesApolipoprotein C-IIIApolipoproteins Abeta-GlobinsCell LineEnhancer Elements, GeneticGene TargetingHumansInterleukin-2 Receptor alpha SubunitMyoD ProteinPolymorphism, Single NucleotideTranscriptional ActivationTranscription FactorsAPOC3 protein, humanapolipoprotein A-IVApolipoprotein C-IIIApolipoproteins Abeta-GlobinsIL2RA protein, humanInterleukin-2 Receptor alpha SubunitMyoD1 myogenic differentiation proteinMyoD ProteinTranscription Factors

Identifiers

PMID34354266
PMCPMC8446310
OpenAlexW3193236546

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.