Cited by 219CRISPR and Genetic EngineeringEpigenetics and DNA MethylationAnimal Genetics and Reproduction

Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein

Open access
Lei, Yong, Zhang, Xiaotian, Su, Jianzhong, Jeong, Mira, Gundry, Michael C., Huang, Yung-Hsin, Zhou, Yubin, Li, Wei +1 more·2017·Nature Communications

Abstract

Comprehensive studies have shown that DNA methylation plays vital roles in both loss of pluripotency and governance of the transcriptome during embryogenesis and subsequent developmental processes. Aberrant DNA methylation patterns have been widely observed in tumorigenesis, ageing and neurodegenerative diseases, highlighting the importance of a systematic understanding of DNA methylation and the dynamic changes of methylomes during disease onset and progression. Here we describe a facile and convenient approach for efficient targeted DNA methylation by fusing inactive Cas9 (dCas9) with an engineered prokaryotic DNA methyltransferase MQ1. Our study presents a rapid and efficient strategy to achieve locus-specific cytosine modifications in the genome without obvious impact on global methylation in 24 h. Finally, we demonstrate our tool can induce targeted CpG methylation in mice by zygote microinjection, thereby demonstrating its potential utility in early development.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ncomms16026

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Additional dCas9-tethered domains have been shown to disrupt enhancer activity.

    “Additional dCas9-tethered domains have been shown to disrupt enhancer activity (e.g. histone demethylase LSD1210, histone deacetylase 3211, and DNA methylators MQ212 or DNMT3A213-215), and could potentially be adapted to large-scale screens.”

    From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [212]

    The Methods (Plasmid construction) identify the paper's dCas9–MQ1 fusion, and the Results (Targeted CpG methylation affects CTCF binding) show that its targeted methylation reduced CTCF binding and altered expression at RUNX1. The paper does not show that dCas9–MQ1 disrupted enhancer activity; it tests CTCF-binding sites instead. Page numbers are unavailable in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Renbaum P.. Cloning, characterization, and expression in Escherichia coli of the gene coding for the CpG DNA methylase from Spiroplasma sp. strain MQ1(M.SssI). Nucleic Acids Res. 18, 1145– 1152 (1990). 2181400 PMC330428

Cited by

Sorted by citations

Authors
Lei, Y., Zhang, X., Su, J., Jeong, M., Gundry, M. C., Huang, Y.-H., Zhou, Y., Li, W., & Goodell, M. A.
Affiliations
  • Baylor College of Medicine (US)
  • Texas A&M University (US)
Corresponding author
Goodell, Margaret A.
Venue
Nature Communications
Published
2017-07-11
Volume
8
Issue
1
Pages
16026-16026
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2735350095
Cited by
218
References
40
Citations by year
2026: 4 · 2025: 20 · 2024: 22 · 2023: 28 · 2022: 26 · 2021: 26 · 2020: 32 · 2019: 24 · 2018: 32 · 2017: 3
FWCI
10.28
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Welch Foundation
  • Cancer Prevention and Research Institute of Texas (CA183252, DK092883, BE-1913, CA125123)
  • Adrienne Helis Malvin Medical Research Foundation
  • Edward P. Evans Foundation
  • Evans Medical Foundation
  • National Institutes of Health (DK092883, CA183252, DK092883, CA125123, CA193466)
  • National Human Genome Research Institute (R01HG007538)
  • National Cancer Institute (F99CA222736, K00CA222736, R01CA183252, R01CA193466, P30CA125123, P50CA126752)
  • National Institute of General Medical Sciences (R01GM112003)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R56DK092883, T32DK060445, R01DK092883)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Keywords
targeted DNA methylation, cytosine methylation, CpG methylation, zygote microinjection, in vivo gene editing, embryonic development, methylome
MeSH terms
Gene Editing, CCCTC-Binding Factor, Animals, Humans, Microinjections, Tenericutes, Recombinant Fusion Proteins, DNA Modification Methylases, CpG Islands, DNA Methylation, K562 Cells, Mice, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review