Evidence map›Paper›PMID 34588447›Full record

ArticleNature communications2021

Unraveling the functional role of DNA demethylation at specific promoters by targeted steric blockage of DNA methyltransferase with CRISPR/dCas9.

Daniel M Sapozhnikov, Moshe Szyf

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

46 citing papers in PubMed, 78 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Development of a prognostic model based on m6A readerTranslational cancer research · 2025
    Article
  9. DNA Methylation in Long-Term Memory.Physiology (Bethesda, Md.) · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Toward DNA-Based Recording of Biological Processes.International journal of molecular sciences · 2024
    Review
  19. Review
  20. Article
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

2 authors at 1 institution in 1 country.

Daniel M SapozhnikovDepartment of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0001-5721-2782
Moshe SzyfDepartment of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada. moshe.szyf@mcgill.ca.ORCID http://orcid.org/0000-0003-3881-8214
McGill University · CA

Funding

CIHR PJT-159583
6 · The paper itself

Abstract

Despite four decades of research to support the association between DNA methylation and gene expression, the causality of this relationship remains unresolved. Here, we reaffirm that experimental confounds preclude resolution of this question with existing strategies, including recently developed CRISPR/dCas9 and TET-based epigenetic editors. Instead, we demonstrate a highly effective method using only nuclease-dead Cas9 and guide RNA to physically block DNA methylation at specific targets in the absence of a confounding flexibly-tethered enzyme, thereby enabling the examination of the role of DNA demethylation per se in living cells, with no evidence of off-target activity. Using this method, we probe a small number of inducible promoters and find the effect of DNA demethylation to be small, while demethylation of CpG-rich FMR1 produces larger changes in gene expression. This method could be used to reveal the extent and nature of the contribution of DNA methylation to gene regulation.

Indexed as

DNA DemethylationEpigenesis, GeneticAnimalsCpG IslandsCRISPR-Cas SystemsDNA MethylationDNA Modification MethylasesFragile X Messenger Ribonucleoprotein 1Gene EditingHEK293 CellsHumansMiceMixed Function OxygenasesNIH 3T3 CellsPromoter Regions, GeneticProto-Oncogene ProteinsDNA Modification MethylasesFMR1 protein, humanFragile X Messenger Ribonucleoprotein 1Mixed Function OxygenasesProto-Oncogene ProteinsRNA, Guide, CRISPR-Cas SystemsSERPIN-B5SerpinsTET1 protein, human

Identifiers

PMID34588447
PMCPMC8481236
OpenAlexW3204151063

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.