ArticleThe Journal of clinical investigation2015
TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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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.
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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.
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Who cites it
85 citing papers in PubMed, 133 citations in OpenAlex.
- Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities.Clinical epigenetics · 2025Review
- Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells.ACS synthetic biology · 2025Article
- The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- Integration of CRISPR/dCas9-Based methylation editing with guide positioning sequencing identifies dynamic changes of mrDEGs in breast cancer progression.Cellular and molecular life sciences : CMLS · 2025Article
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- On correlative and causal links of replicative epimutations.Trends in genetics : TIG · 2025Review
- Comparative epigenomics to clinical trials in human breast cancer and canine mammary tumor.Animal cells and systems · 2025Review
- Effects of DNA methylation and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2024Review
- Reshaping the Landscape of the Genome: Toolkits for Precise DNA Methylation Manipulation and Beyond.JACS Au · 2024Review
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Epigenetic editing for autosomal dominant neurological disorders.Frontiers in genome editing · 2024Review
- DNA methylation-mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation.The Journal of clinical investigation · 2023Article
- Transgenerational Epigenetic DNA Methylation Editing and Human Disease.Biomolecules · 2023Review
- Functional characterization of age-dependent p16 epimutation reveals biological drivers and therapeutic targets for colorectal cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Review
- An Overview of Genome Editing in Cardiovascular and Metabolic Diseases.Advances in experimental medicine and biology · 2023Article
- Efficient generation of epigenetic disease model mice by epigenome editing using the piggyBac transposon system.Epigenetics & chromatin · 2022Article
- Enzyme-free targeted DNA demethylation using CRISPR-dCas9-based steric hindrance to identify DNA methylation marks causal to altered gene expression.Nature protocols · 2022Review
- Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.
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Registered trials
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.