ArticleThe Journal of biological chemistry2012
5'-Cytosine-phosphoguanine (CpG) methylation impacts the activity of natural and engineered meganucleases.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed.
- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- Recent advances in site-specific transgene insertion into the maize genome using recombinases and genome editing endonucleases.Frontiers in plant science · 2025Review
- Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein.Nature communications · 2017Article
- Salient Features of Endonuclease Platforms for Therapeutic Genome Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Quantifying genome-editing outcomes at endogenous loci with SMRT sequencing.Cell reports · 2014Article
- In vitro Inactivation of Latent HSV by Targeted Mutagenesis Using an HSV-specific Homing Endonuclease.Molecular therapy. Nucleic acids · 2014Article
- Novel fluorescent genome editing reporters for monitoring DNA repair pathway utilization at endonuclease-induced breaks.Nucleic acids research · 2014Article
- New frontier in regenerative medicine: site-specific gene correction in patient-specific induced pluripotent stem cells.Human gene therapy · 2013Review
- Article
- Overcoming transcription activator-like effector (TALE) DNA binding domain sensitivity to cytosine methylation.The Journal of biological chemistry · 2012Article
- Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR-Cas9 when targeting the human CCR5 gene.Genetics and molecular biologyArticle
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we asked whether CpG methylation could influence the DNA binding affinity and activity of meganucleases used for genome engineering applications. A combination of biochemical and structural approaches enabled us to demonstrate that CpG methylation decreases I-CreI DNA binding affinity and inhibits its endonuclease activity in vitro. This inhibition depends on the position of the methylated cytosine within the DNA target and was almost total when it is located inside the central tetrabase. Crystal structures of I-CreI bound to methylated cognate target DNA suggested a molecular basis for such inhibition, although the precise mechanism still has to be specified. Finally, we demonstrated that the efficacy of engineered meganucleases can be diminished by CpG methylation of the targeted endogenous site, and we proposed a rational design of the meganuclease DNA binding domain to alleviate such an effect. We conclude that although activity and sequence specificity of engineered meganucleases are crucial parameters, target DNA epigenetic modifications need to be considered for successful gene editions.
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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.