Evidence map›Paper›PMID 31541098›Full record

ArticleNature communications2019

Enhanced CRISPR-based DNA demethylation by Casilio-ME-mediated RNA-guided coupling of methylcytosine oxidation and DNA repair pathways.

Aziz Taghbalout, Menghan Du, Nathaniel Jillette, Wojciech Rosikiewicz, Abhijit Rath, Christopher D Heinen, Sheng Li, Albert W Cheng

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

26 citing papers in PubMed, 50 citations in OpenAlex.

  1. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  2. Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025
    Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Pathways of DNA Demethylation.Advances in experimental medicine and biology · 2022
    Article
  17. Aging · 2021
    Article
  18. Article
  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

8 authors at 3 institutions in 1 country.

Aziz TaghbaloutThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA.
Menghan DuThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA.
Nathaniel JilletteThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA.
Wojciech RosikiewiczThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA.
Abhijit RathCenter for Molecular Oncology, University of Connecticut Health, 263 Farmington Avenue, Farmington, CT, 06030, USA.
Christopher D HeinenCenter for Molecular Oncology, University of Connecticut Health, 263 Farmington Avenue, Farmington, CT, 06030, USA.
Sheng LiThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA.
Albert W ChengThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA. albert.cheng@jax.org.ORCID http://orcid.org/0000-0003-2653-5743
Jackson Laboratory · USMolecular Oncology (United States) · USUniversity of Connecticut · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
Modular Platform for Combinatorial Epigenome ManipulationR01HG009900 · NHGRI · JACKSON LABORATORY · PI ADAMS, MARK D · 2018 to 2022
$3.7M
Mismatch Repair Functions Affected During TumorigenesisR01CA115783 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HEINEN, CHRISTOPHER D. · 2008 to 2012
$1.2M
NCI NIH HHS P30 CA034196NCI NIH HHS R01 CA115783NHGRI NIH HHS R01 HG009900
6 · The paper itself

Abstract

Here we develop a methylation editing toolbox, Casilio-ME, that enables not only RNA-guided methylcytosine editing by targeting TET1 to genomic sites, but also by co-delivering TET1 and protein factors that couple methylcytosine oxidation to DNA repair activities, and/or promote TET1 to achieve enhanced activation of methylation-silenced genes. Delivery of TET1 activity by Casilio-ME1 robustly alters the CpG methylation landscape of promoter regions and activates methylation-silenced genes. We augment Casilio-ME1 to simultaneously deliver the TET1-catalytic domain and GADD45A (Casilio-ME2) or NEIL2 (Casilio-ME3) to streamline removal of oxidized cytosine intermediates to enhance activation of targeted genes. Using two-in-one effectors or modular effectors, Casilio-ME2 and Casilio-ME3 remarkably boost gene activation and methylcytosine demethylation of targeted loci. We expand the toolbox to enable a stable and expression-inducible system for broader application of the Casilio-ME platforms. This work establishes a platform for editing DNA methylation to enable research investigations interrogating DNA methylomes.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsDNA DemethylationDNA Repair5-MethylcytosineCell Cycle ProteinsCell Line, TumorCell ProliferationCRISPR-Cas SystemsDNA-(Apurinic or Apyrimidinic Site) LyaseDNA GlycosylasesDNA MethylationGADD45 ProteinsGene EditingHEK293 CellsHumansMixed Function Oxygenases5-MethylcytosineCell Cycle ProteinsDNA-(Apurinic or Apyrimidinic Site) LyaseDNA GlycosylasesGADD45A protein, humanGADD45 ProteinsMixed Function OxygenasesNEIL2 protein, humanProto-Oncogene ProteinsRNA, Guide, CRISPR-Cas SystemsTET1 protein, human

Identifiers

PMID31541098
PMCPMC6754513
OpenAlexW2973580032

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.