Evidence map›Paper›PMID 31680172›Full record

ArticleNucleic acids research2019

Targeted DNA methylation of neurodegenerative disease genes via homology directed repair.

Christopher P Cali, Daniel S Park, Edward B Lee

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Epigenetic networks coordinate DNA methylation across the genome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.International journal of molecular sciences · 2023
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. 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

3 authors at 1 institution in 1 country.

Christopher P CaliTranslational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Daniel S ParkTranslational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Edward B LeeTranslational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
University of Pennsylvania · US

Funding

Epigenetic Editing of Mutant C9orf72R01NS095793 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI LEE, EDWARD BYUNG-HA · 2016 to 2020
$2.2M
NINDS NIH HHS R01 NS095793
6 · The paper itself

Abstract

DNA methyltransferases (DNMTs) are thought to be involved in the cellular response to DNA damage, thus linking DNA repair mechanisms with DNA methylation. In this study we present Homology Assisted Repair Dependent Epigenetic eNgineering (HARDEN), a novel method of targeted DNA methylation that utilizes endogenous DNA double strand break repair pathways. This method allows for stable targeted DNA methylation through the process of homology directed repair (HDR) via an in vitro methylated exogenous repair template. We demonstrate that HARDEN can be applied to the neurodegenerative disease genes C9orf72 and APP, and methylation can be induced via HDR with both single and double stranded methylated repair templates. HARDEN allows for higher targeted DNA methylation levels than a dCas9-DNMT3a fusion protein construct at C9orf72, and genome-wide methylation analysis reveals no significant off-target methylation changes when inducing methylation via HARDEN, whereas the dCas9-DNMT3a fusion construct causes global off-target methylation. HARDEN is applied to generate a patient derived iPSC model of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) that recapitulates DNA methylation patterns seen in patients, demonstrating that DNA methylation of the 5' regulatory region directly reduces C9orf72 expression and increases histone H3K9 tri-methylation levels.

Indexed as

Amyloid beta-Protein PrecursorAmyotrophic Lateral SclerosisC9orf72 ProteinCell LineCRISPR-Cas SystemsDNA Breaks, Double-StrandedDNA-Cytosine MethylasesDNA DamageDNA MethylationDNA RepairFrontotemporal DementiaGene Knockout TechniquesGenome, HumanHEK293 CellsHistonesHumansAmyloid beta-Protein PrecursorAPP protein, humanC9orf72 ProteinC9orf72 protein, humanDNA-Cytosine MethylasesHistonesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID31680172
PMCPMC7145628
OpenAlexW2986943198

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.