The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
Editing DNA Methylation in the Mammalian Genome
Open accessAbstract
Mammalian DNA methylation is a critical epigenetic mechanism orchestrating gene expression networks in many biological processes. However, investigation of the functions of specific methylation events remains challenging. Here, we demonstrate that fusion of Tet1 or Dnmt3a with a catalytically inactive Cas9 (dCas9) enables targeted DNA methylation editing. Targeting of the dCas9-Tet1 or -Dnmt3a fusion protein to methylated or unmethylated promoter sequences caused activation or silencing, respectively, of an endogenous reporter. Targeted demethylation of the BDNF promoter IV or the MyoD distal enhancer by dCas9-Tet1 induced BDNF expression in post-mitotic neurons or activated MyoD facilitating reprogramming of fibroblasts into myoblasts, respectively. Targeted de novo methylation of a CTCF loop anchor site by dCas9-Dnmt3a blocked CTCF binding and interfered with DNA looping, causing altered gene expression in the neighboring loop. Finally, we show that these tools can edit DNA methylation in mice, demonstrating their wide utility for functional studies of epigenetic regulation.
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“CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) employ catalytically deactivated forms of Cas9 (dCas9) that are fused to transcriptional repressors or activators 29,101 .”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [101]
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In the citing paper
“They are currently being evaluated in preclinical models of PTSD, addiction, and MDD (125, 126).”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [125]
Experimental — accuracy not yet measuredIn the citing paper
“dCas9-TET and dCas9-DNMT3a fusions have been shown to induce effective remodeling of 5mC (Fig. 3) (56).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [56]
In the citing paper
“Similarly, targeted de-methylation with a dCas9-TET fusion protein has been demonstrated (Amabile et al., 2016; Liu et al., 2016), and this strategy could be used to restore an insulated neighborhood whose anchor site is disrupted by aberrant DNA methylation (Figure 8B).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Liu et al., 2016
In the citing paper
“Indeed, targeted methylation of a neighborhood anchor site with a dCas9-DNA-metyltransferase-3 fusion protein has been shown to disrupt the neighborhood (Figure 8A) (Liu et al., 2016).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Liu et al., 2016
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Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · cited 2×
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InfluentialModel-based Analysis of ChIP-Seq (MACS)
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Self-citationA Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
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“Clustered regularly interspaced palindromic repeats (CRISPR), a type II bacterial adaptive immune system, has been modified to target the Cas9 nuclease to the desired genomic loci with sequence-specific guide RNAs for genome editing (Cong et al., 2013; Jinek et al., 2012; Mali et al., 2013).”
InfluentialMultiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339 · cited 2×
“Clustered regularly interspaced palindromic repeats (CRISPR), a type II bacterial adaptive immune system, has been modified to target the Cas9 nuclease to the desired genomic loci with sequence-specific guide RNAs for genome editing (Cong et al., 2013; Jinek et al., 2012; Mali et al., 2013).”
Self-citationRNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210 · cited 2×
“Clustered regularly interspaced palindromic repeats (CRISPR), a type II bacterial adaptive immune system, has been modified to target the Cas9 nuclease to the desired genomic loci with sequence-specific guide RNAs for genome editing (Cong et al., 2013; Jinek et al., 2012; Mali et al., 2013).”
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124 · cited 2×
“Mammalian DNA methylation at 5-cytosine plays critical roles in many biological processes, including genomic imprinting, cell fate determination, chromatin architecture organization, and regulation of gene expression (Bird, 2002; Jaenisch and Bird, 2003; Smith and Meissner, 2013).”
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829 · cited 2×
“…are constrained within larger CTCF-mediated loops called insulated neighborhoods (Dowen et al., 2014; Ji et al., 2016; Phillips-Cremins et al., 2013), which, in turn, can form clusters of loops that contribute to topologically associating domains (TADs) (Dixon et al., 2012; Nora et al., 2012).”
Jaenisch, R., & Bird, A. (2003) · Nature Genetics · doi:10.1038/ng1089 · Cited by 6,325 · cited 3×
“Genetic studies have revealed that DNA methylation is essential for mammalian development and adaptation to environmental signals (Jaenisch and Bird, 2003).”
Self-citationRepurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression
Qi, L. S., Larson, M. H., Gilbert, L. A., Doudna, J. A., Weissman, J. S., Arkin, A. P., & Lim, W. A. (2013) · Cell · doi:10.1016/j.cell.2013.02.022 · Cited by 5,016 · cited 2×
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Human DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673 · cited 2×
“Owing to the advancement in sequencing technologies, single-nucleotide resolution methylation maps for many types of human and mouse cells and tissues have been depicted (Lister et al., 2009, 2013).”
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A tour of 3D genome with a focus on CTCF
Wang, D. C., Wang, W. Y., Zhang, L., & Wang, X. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.07.020 · Cited by 25
Genome editing in the mammalian brain using the CRISPR–Cas system
Nishiyama, J. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.07.003 · Cited by 25
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Exploiting epigenetics for the treatment of inborn errors of metabolism
Rutten, M. G. S., Rots, M. G., & Oosterveer, M. H. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12093 · Cited by 26
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Liu, Y., Ma, S., Chang, J., Zhang, T., Chen, X., Liang, Y., & Xia, Q. (2019) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2019.04.013 · Cited by 24
Perspectives for epigenetic editing in crops
Selma, S., & Orzáez, D. (2021) · Transgenic Research · doi:10.1007/s11248-021-00252-z · Cited by 24
Pandey, M., Ojha, D., Bansal, S., Rode, A. B., & Chawla, G. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101003 · Cited by 23
Yang, X., Bui, T. A., Mei, H., Aksoy, Y. A., Deng, F., Hutvágner, G., & Deng, W. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202402630 · Cited by 28
Therapeutic application of the CRISPR system: current issues and new prospects
Lee, M., & Kim, S. (2019) · Human Genetics · doi:10.1007/s00439-019-02028-2 · Cited by 23
Chemical and Light Inducible Epigenome Editing
Zhao, W., Wang, Y., & Liang, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030998 · Cited by 23
p53-intact cancers escape tumor suppression through loss of long noncoding RNA Dino
Marney, C. B., Anderson, E. S., Adnan, M., Peng, K.-L., Hu, Y., Weinhold, N., & Schmitt, A. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109329 · Cited by 22
Dual methylation and hydroxymethylation study of alcohol use disorder
Clark, S. L., Chan, R. F., Zhao, M., Xie, L. Y., Copeland, W., Penninx, B. W. J. H., Åberg, K. A., & van den Oord, E. J. C. G. (2021) · Addiction Biology · doi:10.1111/adb.13114 · Cited by 23
McFadden, V. C., Shalaby, R. E., Iram, S., Oropeza, C. E., Landolfi, J. A., Lyubimov, A. V., Maienschein‐Cline, M., Green, S. J., Kaestner, K. H., & McLachlan, A. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006239 · Cited by 23
Greenfield, R., Tabib, A., Keshet, I., Moss, J., Sabag, O., Goren, A., & Cedar, H. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804755115 · Cited by 25
“The general picture that emerges from these studies is that the addition of methyl groups to DNA can only take place on gene regions that are not selected for transcription and that this modification then serves to prevent activation, perhaps by decreasing their accessibility to protein factors (9, 34).”
BackgroundEpigenetics and noncoding RNA: Recent developments and future therapeutic opportunities
Henshall, D. C. (2019) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2019.06.002 · Cited by 23
Advances in the Delivery and Development of Epigenetic Therapeutics for the Treatment of Cancer
Ghosh, A., Himaja, A., Biswas, S., Kulkarni, O. P., & Ghosh, B. (2023) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c00610 · Cited by 23
Targeted demethylation and activation of NLRC5 augment cancer immunogenicity through MHC class I
Sun, X., Watanabe, T., Oda, Y., Shen, W., Ahmad, A. M., Ouda, R., de Figueiredo, P., Kitamura, H., Tanaka, S., & Kobayashi, K. S. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2310821121 · Cited by 22
“Similar approaches have successfully induced targeted demethylation (24–27).”
BackgroundMethodEpigenome editing based treatment: Progresses and challenges
Yuan, L., Xiong, Y., Zhang, Y., Gu, S., & Lei, Y. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.08.047 · Cited by 30
“11 Therefore, combined treatments that pair ncRNAs with targeted epigenome editors through endogenous DNMTs recruitment, such as CHARM, represent a promising strategy that warrants further exploration for human disease applications.”
The evolving CRISPR technology
Yan, M., & Li, J. (2019) · Protein & Cell · doi:10.1007/s13238-019-0645-9 · Cited by 22
Novel methylation-driven genes identified as prognostic indicators for lung squamous cell carcinoma.
Li, Y., Gu, J., Xu, F., Zhu, Q., Ge, D., & Lu, C. (2019) · PubMed Central · Cited by 22
A comprehensive overview of CRISPR/Cas 9 technology and application thereof in drug discovery
Khurana, A., Sayed, N., Singh, V., Khurana, I., Allawadhi, P., Rawat, P. S., Navik, U., Pasumarthi, S. K., Bharani, K. K., & Weiskirchen, R. (2022) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30329 · Cited by 22
Fontana, L., Alahouzou, Z., Miccio, A., & Antoniou, P. (2023) · Genes · doi:10.3390/genes14030577 · Cited by 27
Long-range gene regulation in hormone-dependent cancer
Tettey, T. T., Rinaldi, L., & Hager, G. L. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00603-4 · Cited by 23
Stem cells and genome editing: approaches to tissue regeneration and regenerative medicine
Takata, N., & Eiraku, M. (2017) · Journal of Human Genetics · doi:10.1038/s10038-017-0348-0 · Cited by 23
Modeling epigenetic modifications in renal development and disease with organoids and genome editing
del Pozo, C. H., Garreta, E., Belmonte, J. C. I., & Montserrat, N. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.035048 · Cited by 23
“Additionally, Liu and colleagues have repurposed the CRISPR/Cas9 system to edit DNA methylation by fusing dCas9 with TET1 and DNMT3A (Box 2; Fig.”
InfluentialRicci, R., & Colasante, G. (2021) · Developmental Neuroscience · doi:10.1159/000515845 · Cited by 23
Vijayraghavan, S., & Kantor, B. (2017) · Journal of Visualized Experiments · doi:10.3791/56915 · Cited by 20
Applications of the CRISPR-Cas9 system in kidney research
Higashijima, Y., Hirano, S., Nangaku, M., & Nureki, O. (2017) · Kidney International · doi:10.1016/j.kint.2017.01.037 · Cited by 22
Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems
Rehbach, K., Fernando, M. B., & Brennand, K. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0518-19.2019 · Cited by 22
Climate change shapes the future evolution of plant metabolism
Xu, S. Y., & Weng, J. (2020) · Advanced Genetics · doi:10.1002/ggn2.10022 · Cited by 20
“Recent development of CRISPR/Cas9-based epigenome-editing tools therefore affords a new avenue to alter crop metabolic traits or stress resistance without changing the DNA sequence.(127)”
BackgroundAdvances and Opportunities in Epigenetic Chemical Biology
Beyer, J. N., Raniszewski, N. R., & Burslem, G. M. (2020) · ChemBioChem · doi:10.1002/cbic.202000459 · Cited by 23
CRISPR-Based Approaches for the High-Throughput Characterization of Long Non-Coding RNAs
Hazan, J. M., & Bester, A. C. (2021) · Non-Coding RNA · doi:10.3390/ncrna7040079 · Cited by 22
CRISPR/Cas9 technology: applications in oocytes and early embryos
Zhang, Y., Yin, T., & Zhou, L. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04610-9 · Cited by 26
“For example, studies have shown that the fusion of dCas9 with DNMT3a or TET1 allows for the silencing or activating of endogenous reporters respectively, by targeting promoter sequences [61] (Fig.”
BackgroundMethodInfluentialEngineering nucleic acid chemistry for precise and controllable CRISPR/Cas9 genome editing
Cai, W., & Wang, M. (2019) · 中国科学通报：英文版 · doi:10.1016/j.scib.2019.07.035 · Cited by 21
“Catalytically inactive Cas9 (dCas9) and Nickase are also instrumental recently in transcriptional regulation [13,14], base editing [15], epigenetic editing [16], etc.”
BackgroundYang, Y., Dai, Y., Yang, X., Wu, S., & Wang, Y. (2021) · Biomolecules · doi:10.3390/biom11060781 · Cited by 21
The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation
Monteagudo, A., Albert, J. R., Scarpa, M., Noordermeer, D., & Greenberg, M. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae724 · Cited by 22
“Not only are these powerful tools to modify CTCF binding in cell culture systems, as described here and elsewhere ( 98 , 122 , 123 ), but they can also be implemented in vivo ( 123 ).”
BackgroundModulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing
Valcárcel, G., López-Rubio, A. V., Lazarenkov, A., Berenguer, C., Calafell-Segura, J., Rodríguez‐Ubreva, J., Ballestar, E., & Sardina, J. L. (2025) · Science Advances · doi:10.1126/sciadv.adt1644 · Cited by 23
Transcriptional enhancers: from prediction to functional assessment on a genome-wide scale
Tobias, I. C., Abatti, L. E., Moorthy, S. D., Mullany, S., Taylor, T., Khader, N., Filice, M., & Mitchell, J. A. (2020) · Genome · doi:10.1139/gen-2020-0104 · Cited by 25
“Fusion of the DNA methyltransferase 3A (DNMT3A) catalytic domain to either dCas9 directly (dCas9-DNMT3A) (Figure 3G) (Liu et al. 2016; Vojta et al. 2016), or recruitment of antibody-tagged DNMT3A to repeating polypeptides chains (sunTag) fused to dCas9 (Figure 3J) (Huang et al. 2017; Pflueger et…”
BackgroundMethodInfluentialWang, K., Dai, R., Xia, Y., Tian, J., Jiao, C., Mikhailova, T., Zhang, C., Chen, C., & Liu, C. (2021) · Epigenetics · doi:10.1080/15592294.2021.1993607 · Cited by 23
“Chromatin structure alterations can also change the relationship between DNAm and gene expression [33].”
BackgroundInfluentialLongitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy
Witasp, A., Luttropp, K., Qureshi, A. R., Barany, P. F., Heimbürger, O., Wennberg, L. M., Ekström, T. J., Shiels, P. G., Stenvinkel, P., & Nordfors, L. (2022) · Scientific Reports · doi:10.1038/s41598-021-04321-5 · Cited by 20
CRISPR-Based Genome-Editing Tools for Huntington’s Disease Research and Therapy
Qin, Y., Li, S., Li, X., & Yang, S. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00880-3 · Cited by 24
Georgieva, A. M., Guo, X., Bartkuhn, M., Günther, S., Künne, C., Smolka, C., Atzberger, A., Gärtner, U., Mamchaoui, K., Bober, E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31798-z · Cited by 20
Epigenetic and epitranscriptomic regulation of axon regeneration
Cheng, Y., Song, H., Ming, G., & Weng, Y. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02028-9 · Cited by 21
“Similarly, engineered CRISPR/dCas9-Dnmt3a or dCas9-Tet1 system has been established and successfully demonstrate DNA methylation or demethylation of targeted loci, respectively [85].”
BackgroundChen, Y., Luo, X. L., Kang, R., Cui, K., Ou, J., Zhang, X., & Liang, P. (2023) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2023.07.007 · Cited by 23
Alex, K., & Winkler, E. C. (2023) · Journal of Medical Ethics · doi:10.1136/jme-2022-108888 · Cited by 20
Epigenetic Memory of Stress Responses in Plants
Kumar, S. (2018) · Cited by 20
Kawahori, K., Hashimoto, K., Yuan, X., Tsujimoto, K., Hanzawa, N., Hamaguchi, M., Kase, S., Fujita, K., Tagawa, K., Okazawa, H., et al. (2018) · Thyroid · doi:10.1089/thy.2017.0331 · Cited by 20
“Previous Previous studies suggested that DNA demethylation of the promoter region of Bdnf exon IV contributes to Bdnf expression in neurons, and MeCP2 and TETs may induce DNA methylation and demethylation, respectively (56–58).”
CTCF and cellular heterogeneity
Ren, G., & Zhao, K. (2019) · Cell & Bioscience · doi:10.1186/s13578-019-0347-2 · Cited by 20
“Targeting of dCas9-Dnmt3a to the CTCF binding site bordering the miR290, Pou5f1 gene loops blocked CTCF anchoring, resulted in significantly increased interaction frequency between superenhancers and newly activated genes (Nlrp12, H2Q10) in the neighboring loop, and accompanied by increased expression of Nlrp12, H2Q10…”
BackgroundEditing DNA Methylation in Mammalian Embryos
Yamazaki, T., Hatano, Y., Taniguchi, R., Kobayashi, N., & Yamagata, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020637 · Cited by 22
“On the other hand, other groups have reported that the dCas9–TET1 system is sufficient to decrease DNA methylation in target loci [9,28,32,45,46].”
BackgroundGenomics and epigenomics of addiction
Maldonado, R. J., Calvé, P., García‐Blanco, A., Domingo‐Rodriguez, L., Senabre, E., & Martín‐García, E. (2021) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32843 · Cited by 24
“For instance, CRISPR/Cas9 has been used to target methyl-CpG-binding proteins (Swiech et al., 2015), and Cas9 has also been used after its fusion with DNA methylating enzymes to edit the methylation profile of specific enhancers and promoters (Liu et al., 2016).”
MethodBalance between Retroviral Latency and Transcription: Based on HIV Model
Pluta, A., Jaworski, J. P., & Cortés-Rubio, C. N. (2020) · Pathogens · doi:10.3390/pathogens10010016 · Cited by 22
“The dCas9TET1 fusion protein was capable of reactivating the GFP reporter gene fused to the Snrpn promoter, by inducing a 90% decrease in the DNA methylation levels in this promoter [183].”
BackgroundCortes, L. R., Cisternas, C. D., Cabahug, I. N. K. V., Mason, D., Ramlall, E. K., Castillo‐Ruiz, A., & Forger, N. G. (2021) · Neuroendocrinology · doi:10.1159/000519671 · Cited by 23
Single-Cell Epigenomics Reveals Mechanisms of Cancer Progression
LaFave, L. M., Savage, R. E., & Buenrostro, J. D. (2022) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-070620-094453 · Cited by 19
Dissecting Plant Gene Functions Using CRISPR Toolsets for Crop Improvement
Zhang, R., Li, B., Yang, Z.-G., Huang, J., Sun, W.-H., Bhanbhro, N., Liu, W., & Chen, K. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c01754 · Cited by 20
Sapozhnikov, D. M., & Szyf, M. (2022) · Nature Protocols · doi:10.1038/s41596-022-00741-3 · Cited by 21
Multiplexed engineering and precision gene editing in cellular immunotherapy
Biederstädt, A., Manzar, G. S., & Daher, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1063303 · Cited by 19
Canalizing cell fate by transcriptional repression
Lim, B., Domsch, K., Mall, M., & Lohmann, I. (2024) · Molecular Systems Biology · doi:10.1038/s44320-024-00014-z · Cited by 19
“Targeted DNA demethylation of the Myod1 enhancer using a dCas9-Tet1 fusion construct has also been shown to further enhance fi broblast-to-muscle cell reprogramming by activating Myod1 expression (Liu et al, 2016).”
MethodTargeting the epigenome with advanced delivery strategies for epigenetic modulators
Guha, S., Jagadeesan, Y., Pandey, M. M., Mittal, A., & Chitkara, D. (2024) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10710 · Cited by 22
Neuronal Dnmt1 Deficiency Attenuates Diet-Induced Obesity in Mice
Bruggeman, E. C., Garretson, J. T., Wu, R., Shi, H., & Xue, B. (2017) · Endocrinology · doi:10.1210/en.2017-00267 · Cited by 19
St-Cyr, S., & McGowan, P. O. (2017) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2017.12.003 · Cited by 19
Viral Expression of Epigenome Editing Tools in Rodent Brain Using Stereotaxic Surgery Techniques
Hamilton, P. J., Lim, C. J., Nestler, E. J., & Heller, E. A. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7774-1_10 · Cited by 19
A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing
Sun, H., Li, F., Liu, J., Yang, F., Zeng, Z., Lv, X., Tu, M., Liu, Y., Ge, X., Liu, C., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.05.021 · Cited by 19
Blossom of CRISPR technologies and applications in disease treatment
Liu, H., Wang, L., & Luo, Y. (2018) · Synthetic and Systems Biotechnology · doi:10.1016/j.synbio.2018.10.003 · Cited by 19
“dCas9 DNA methyltransferase domain dCas9-DNMT3A DNA methylation [101]”
BackgroundTagliafierro, L., Ilich, E., Moncalvo, M., Gu, J. T., Sriskanda, A., Grenier, C., Murphy, S. K., Chiba‐Falek, O., & Kantor, B. (2019) · Journal of Visualized Experiments · doi:10.3791/59241 · Cited by 19
Aberrant DNA methylation defines isoform usage in cancer, with functional implications
Chen, Y.-C., & Elnitski, L. L. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007095 · Cited by 19
CRISPR genome engineering for retinal diseases
Kantor, A., McClements, M. E., Peddle, C. F., Fry, L. E., Salman, A., Cehajic‐Kapetanovic, J., Xue, K., & MacLaren, R. E. (2021) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2021.01.024 · Cited by 19
Genome-wide quantification of the effects of DNA methylation on human gene regulationPreprint
Lea, A. J., Vockley, C. M., Johnston, R. A., Carpio, C. A. D., Barreiro, L. B., Reddy, T. E., & Tung, J. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/146829 · Cited by 19
Bearer, E. L., & Mulligan, B. S. (2018) · Current Genomics · doi:10.2174/1389202919666180307150508 · Cited by 19
Epigenetic changes in status epilepticus
Henshall, D. C. (2018) · Epilepsia · doi:10.1111/epi.14502 · Cited by 18
“In the future, it may be possible to use genome editing tools to directly manipulate DNA methylation at specific sites in the genome.(22)”
BackgroundDevelopment and Characterization of a Modular CRISPR and RNA Aptamer Mediated Base Editing System
Collantes, J. C., Tan, V. M., Xu, H., Ruiz-Urigüen, M., Alasadi, A., Guo, J., Tao, H., Su, C., Tyc, K. M., Selmi, T., et al. (2021) · The CRISPR Journal · doi:10.1089/crispr.2020.0035 · Cited by 18
Auditing the Editor: A Review of Key Translational Issues in Epigenetic Editing
Huerne, K., Palmour, N., Wu, A. R., Beck, S., Berner, A., Siebert, R., & Joly, Y. (2022) · The CRISPR Journal · doi:10.1089/crispr.2021.0094 · Cited by 19
The identification and validation of EphA7 hypermethylation, a novel biomarker, in cervical cancer
Zhang, W., Cao, H., Yang, J., Zhao, J. T., Liang, Z., Kang, X., & Wang, R. (2022) · BMC Cancer · doi:10.1186/s12885-022-09653-7 · Cited by 20
“Fuw-dCas9-Tet1CD (#84475), Fuw-dCas9-Tet1CD_IM (#84479), Fuw-dCas9-DNMT3a (#84476) and Fuw-dCas9-DNMT3a_IM (#84478) plasmids were purchased from Addgene [30].”
BackgroundMethodInfluentialSapozhnikov, D. M., & Szyf, M. (2023) · Biomedicines · doi:10.3390/biomedicines11051238 · Cited by 18
“In 2016, four independent groups developed CRISPR/dCas9-based systems for targeted DNA demethylatio ; those that fuse [41,59] or recruit [60,61] the catalytic domain of TET1 with CRISPR/dCas9.”
BackgroundTuning Methylation-Dependent Silencing Dynamics by Synthetic Modulation of CpG Density
Ma, Y., Budde, M. W., Zhu, J., & Elowitz, M. B. (2023) · ACS Synthetic Biology · doi:10.1021/acssynbio.3c00078 · Cited by 18
Xiao, D., Fang, L., Liu, Z., He, Y., Ying, J., Qin, H., Lu, A., Shi, M., Li, T., Zhang, B., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci168558 · Cited by 18
Liu, X., Zhao, N.-N., Yuan, H., Liu, M., Liu, M., & Zhang, C. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115966 · Cited by 18
Self-citationLaha, S. D., Kundu, A., & Podder, S. (2024) · Planta · doi:10.1007/s00425-024-04379-1 · Cited by 18
“This emerging technique has already been applied to combat biotic stresses including fungal, bacterial, viral diseases (Li et al. 2022), and insect pests (Liu et al. 2016).”
Epigenetics of Hypertensive Nephropathy
Zhang, Y., Arzaghi, H., Ma, Z., Roye, Y., & Musah, S. (2024) · Biomedicines · doi:10.3390/biomedicines12112622 · Cited by 20
“Conversely, Liu et al. designed dCas9-TET1 to achieve DNA demethylation in the promoter region of brain-derived neurotrophic factor (BDNF) [308].”
Modeling Cancer in the CRISPR Era
Ventura, A., & Dow, L. E. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050455 · Cited by 18
“For example, targeted methylation of CTCF binding sites can disrupt DNA looping and alter gene expression in neighboring regions (Liu et al. 2016).”
BackgroundMillette, K., & Georgia, S. K. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0947-3 · Cited by 18
Emerging Concepts in Innate Immunity
Pelka, K., & Nardo, D. D. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7519-8_1 · Cited by 19
Piecing together cis‐regulatory networks: insights from epigenomics studies in plants
Huang, S. C., & Ecker, J. R. (2017) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1411 · Cited by 19
“This hypothesis may be investigated by comparing TF binding profiles by DAP-seq on genomic DNA from wild-type and methyltransferase mutants, or by precise methylation editing of known target sites.(183) Lastly, transcriptional output at individual genes is the result of multiple levels of regulation, which may be infl…”
MethodA Photo‐responsive Small‐Molecule Approach for the Opto‐epigenetic Modulation of DNA Methylation
Nguyen, H. P., Stewart, S. K., Kukwikila, M. N., Jones, S. F., Offenbartl‐Stiegert, D., Mao, S.-Q., Balasubramanian, S., Beck, S., & Howorka, S. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201901139 · Cited by 18
Potential of Epigenetic Therapy for Prader-Willi Syndrome
Wang, S. E., & Jiang, Y. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.07.002 · Cited by 18
Odell, S. C., Taki, F., Klein, S. L., Chen, R. J., Levine, O. B., Skelly, M. J., Nabila, A., Brindley, E., Toth, J. G., Dündar, F., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107789 · Cited by 17
“Epigenetic editing (Liu et al., 2016) could help in understanding how individual epialleles affect spicing and isoform-specific gene expression.”
Xu, B., Liu, C., Zhang, H., Zhang, R., Tang, M., Huang, Y., Li, J., Xu, L., Hu, C., & Jia, W. (2021) · JCI Insight · doi:10.1172/jci.insight.149969 · Cited by 20
“We have therefore not only elucidated a potentially new mediator between CREB1 and skeletal muscle hypertrophy but also provided a potentially new target to treat muscle waste and metabolic disorders using technologies designed to manipulate DNA methylation at specific genomic loci (54).”
A Lexicon of DNA Modifications: Their Roles in Embryo Development and the Germline
Zhu, Q., Stöger, R. J., & Alberio, R. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00024 · Cited by 21
Chromatin modification factors in plant pathogenic fungi: Insights from Ustilago maydis
Elías-Villalobos, A., Barrales, R. R., & Ibeas, J. I. (2019) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2019.04.006 · Cited by 18
The Expanding Class 2 CRISPR Toolbox: Diversity, Applicability, and Targeting Drawbacks
Dastjerdi, A. H., Newman, A., & Burgio, G. (2019) · BioDrugs · doi:10.1007/s40259-019-00369-y · Cited by 18
Liu, R., Peng, X.-P., Newman, D. J., Purchase, D., Li, G., & Kusari, S. (2025) · Natural Product Reports · doi:10.1039/d5np00028a · Cited by 17
CRISPR-mediated promoter de/methylation technologies for gene regulation
Sung, C. K., & Yim, H. (2020) · Archives of Pharmacal Research · doi:10.1007/s12272-020-01257-8 · Cited by 18
The Prognostic Value and Mechanisms of TMEM16A in Human Cancer
Chen, W., Gu, M., Gao, C., Chen, B., Yang, J., Xie, X., Wang, X., Sun, J. F., & Wang, J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.542156 · Cited by 17
El-Harakeh, M., Saliba, J. L., Aldeen, K. S., Haidar, M., El‐Hajjar, L., Awad, M. K., Hashash, J. G., Shirinian, M., & El-Sabban, M. E. (2022) · World Journal of Gastroenterology · doi:10.3748/wjg.v28.i40.5845 · Cited by 17
THOR is a targetable epigenetic biomarker with clinical implications in breast cancer
Apolónio, J. D., Dias, J. S., Fernandes, M. T., Komosa, M., Lipman, T., Zhang, C. H., Leao, R. R. N., Lee, D., Nunes, N. M., Maia, A.-T., et al. (2022) · Clinical Epigenetics · doi:10.1186/s13148-022-01396-3 · Cited by 19
“…plasmid, #84,475), dCas9-TET-IN (Addgene plasmid, #84,479) and pgRNA-modified (Addgene plasmid, #84,477) plasmids, a gift from Dr. Rudolf Jaenisch (Liu et al., 2016), and a second approach based in a dCas9 fused to a SunTag was used to recruit multiple copies of an antibody fused to the TET1…”
MethodCRISPR activation and interference as investigative tools in the cardiovascular system
Carroll, M. S., & Giacca, M. (2022) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2022.106348 · Cited by 20
“In contrast, a member of the Ten-Eleven Translocation dioxygenase enzyme family (TET1) is often used with dCas9 to increase transcription by catalysing the demethylation of DNA (Liu et al., 2016).”
Engineering CRISPR/Cas-based nanosystems for therapeutics, diagnosis and bioimaging
Song, N., Li, S., Lv, Z., Ding, X., Li, F., & Yang, D. (2023) · Chinese Chemical Letters · doi:10.1016/j.cclet.2023.108134 · Cited by 16
Implication of DNA methylation during lifestyle mediated weight loss
Aurich, S., Müller, L., Kovacs, P. L., & Keller, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1181002 · Cited by 16
Rinonos, S. Z., Li, T., Pianka, S. T., Prins, T. J., Eldred, B. S. C., Kevan, B. M., Liau, L. M., Nghiemphu, P. L., Cloughesy, T. F., & Lai, A. (2024) · Journal of Neuro-Oncology · doi:10.1007/s11060-023-04531-z · Cited by 17
“Given reported enhanced efficiency of d3A-mediated methylation using multiple sgRNAs broadening target regions [16, 17, 29–32], we designed four sgRNAs with specific homology to MGMT regions encompassing promoter, enhancer and exon 1 regions, within a GFP-tagged lentiviral plasmid (Fig.”
BackgroundMethodRecent advances and current status of gene therapy for epilepsy
Cai, A., Gao, K., Zhang, F., & Jiang, Y. (2024) · World Journal of Pediatrics · doi:10.1007/s12519-024-00843-w · Cited by 19
“One effective method is by fusing dCas9 with epigenetic modification enzymes [such as dCas9-DNA methyltransferases 3A (DNMT3A) and dCas9-ten-eleventranslocation protein 1 (TET1)] to directly catalyze the epigenetic modification of DNA or histones, thereby regulating gene expression [116, 117].”
Unlocking the epigenetic code of T cell exhaustion
Wu, J., & Shi, H. (2017) · Translational Cancer Research · doi:10.21037/tcr.2017.03.02 · Cited by 17
“It has also been observed in CD8 + T cells from leukemia patients that the PD-1 expression level was augmented in accordance with a decrease in DNA methylation levels in a distal regulatory region of human PDCD1 (7).”
Influential
Metadata
- Authors
- Liu, X. S., Wu, H., Ji, X., Stelzer, Y., Wu, X., Czauderna, S., Shu, J., Dadon, D., Young, R. A., & Jaenisch, R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Jagiellonian University (PL)
- Corresponding author
- Jaenisch, Rudolf
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 167
- Issue
- 1
- Pages
- 233-247.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5062609
- OpenAlex
- W2521981506
- Cited by
- 1,224
- References
- 58
- Citations by year
- 2026: 98 · 2025: 104 · 2024: 98 · 2023: 107 · 2022: 104 · 2021: 137 · 2020: 124 · 2019: 155 · 2018: 161 · 2017: 123 · 2016: 11
- FWCI
- 77.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- Damon Runyon Cancer Research Foundation
- Helen Hay Whitney Foundation
- National Alliance for Research on Schizophrenia and Depression
- Narodowym Centrum Nauki
- National Institutes of Health
- National Human Genome Research Institute (R01HG002668)
- National Cancer Institute (R37CA084198, P30CA014051)
- National Institute of General Medical Sciences (R01GM114864, T32GM007287)
- National Institute of Neurological Disorders and Stroke (R01NS088538)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD045022, R37HD045022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- TET1, DNMT3A, dCas9, promoter activation, gene silencing, BDNF promoter, DNA looping, epigenetic regulation
- MeSH terms
- Gene Editing, CCCTC-Binding Factor, CRISPR-Associated Protein 9, DNA Methyltransferase 3A, Animals, Bacterial Proteins, Cell Line, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Endonucleases, Enhancer Elements, Genetic, Neurons, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Repressor Proteins, Genome, MyoD Protein, CpG Islands, DNA Methylation, Brain-Derived Neurotrophic Factor, Epigenesis, Genetic, Mice, Clustered Regularly Interspaced Short Palindromic Repeats
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