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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STAR: ultrafast universal RNA-seq aligner
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“STAR+METHODS Detailed methods are provided in the online version of this paper and include the following: d KEY RESOURCES TABLE d CONTACT FOR REAGENT AND RESOURCE SHARING d EXPERIMENTAL MODEL AND SUBJECT DETAILS B Mouse lines and breeding strategies B Mouse primary cortical neuron culture, EDU labeling, and neural ind…”
InfluentialModel-based Analysis of ChIP-Seq (MACS)
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“Peaks are called using MACS (Zhang et al., 2008) with default settings.”
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×
“…activator/suppressor, chromatin modifier, and green fluorescence protein to regulate gene expression, to modify chromatin, and to image genomic loci respectively (Chen et al., 2013; Gilbert et al., 2013; Hilton et al., 2015; Jinek et al., 2012; Konermann et al., 2015; Qi et al., 2013).”
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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CRISPR-based tools for plant genome engineering
Silva, N. V. E., & Patron, N. J. (2017) · Emerging Topics in Life Sciences · doi:10.1042/etls20170011 · Cited by 17
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Sandoval, A., Elahi, H., & Ploski, J. E. (2020) · eNeuro · doi:10.1523/eneuro.0419-19.2020 · Cited by 18
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Recent advances in CRISPR technologies for genome editing
Song, M., & Koo, T. (2021) · Archives of Pharmacal Research · doi:10.1007/s12272-021-01336-4 · Cited by 18
Locus-Specific DNA Methylation Editing in Melanoma Cell Lines Using a CRISPR-Based System
Smith, J., Banerjee, R., Waly, R., Urbano, A., Gimenez, G., Day, R. C., Eccles, M. R., Weeks, R. J., & Chatterjee, A. (2021) · Cancers · doi:10.3390/cancers13215433 · Cited by 19
Central Neuroepigenetic Regulation of the Hypothalamic–Pituitary–Adrenal Axis
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Early postnatal overnutrition accelerates aging-associated epigenetic drift in pancreatic islets
Li, G., Petkova, T. D., Laritsky, E., Kessler, N. J., Baker, M. S., Zhu, S., & Waterland, R. A. (2019) · Current Zoology · doi:10.1093/eep/dvz015 · Cited by 18
Cellular Models of Aging and Senescence
Kim, B., Lee, D. I., Basisty, N., & Dai, D.-F. (2025) · Cells · doi:10.3390/cells14161278 · Cited by 16
“Similarly, targeted epigenetic modifications utilizing CRISPR-dCas9-TET1 systems have also demonstrated localized rejuvenation effects at aging-associated genomic loci [32,33].”
The role of TET proteins in stress-induced neuroepigenetic and behavioural adaptations
Dick, A., & Chen, A. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100352 · Cited by 17
Rasmussen, E. M. K., Seier, K. L., Pedersen, I. K., Kreibich, C. D., Amdam, G. V., Münch, D., & Dahl, J. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-98614-4 · Cited by 17
“Although variations of the CRISPR/Cas9 system have been engineered to specifically modulate the methylome(Lei et al., 2017; Morita et al., 2016) (Liu et al., 2016; Vojta et al., 2016), these techniques are not readily available for human therapy as they would either need a very specific target…”
BackgroundReprogramming cell fate with artificial transcription factors
Heiderscheit, E. A., Eguchi, A., Spurgat, M. C., & Ansari, A. Z. (2018) · FEBS Letters · doi:10.1002/1873-3468.12993 · Cited by 18
Dalziel, A. C., Tirbhowan, S., Drapeau, H. F., Power, C., Jonah, L., Gbotsyo, Y. A., & Dion‐Côté, A. (2020) · Evolutionary Applications · doi:10.1111/eva.12975 · Cited by 19
“One option will be to conduct epigenetic editing of candidate sites and then test for effects on gene regulation and candidate phenotypes (Josipović et al., 2019; Liu et al., 2016).”
BackgroundJavaid, N., Pham, T. L. H., & Choi, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010397 · Cited by 18
Huang, L., Liao, Z., Liu, Z., Chen, Y., Huang, T., & Xiao, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.900825 · Cited by 16
Han, Z., Ma, F., & Zhang, C. (2023) · Analytica Chimica Acta · doi:10.1016/j.aca.2023.340996 · Cited by 16
Yamada, Y., & Yamada, Y. (2018) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.94.016 · Cited by 18
Concurrent genome and epigenome editing by CRISPR-mediated sequence replacement
Alexander, J., Findlay, G. M., Kircher, M., & Shendure, J. (2019) · BMC Biology · doi:10.1186/s12915-019-0711-z · Cited by 16
Genomic Targeting of TET Activity for Targeted Demethylation Using CRISPR/Cas9
Nguyen, T. V., & Lister, R. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1294-1_10 · Cited by 16
Integration of CRISPR-engineering and hiPSC-based models of psychiatric genomics
Matos, M. R., Ho, S., Schrode, N., & Brennand, K. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103532 · Cited by 15
“, 2013), epigenetic modulation (Liu et al., 2016), single base editing (Komor et al.”
BackgroundDNA methylation: The epigenetic mechanism of Alzheimer's disease
Qin, H., Liu, J., Fang, C., Deng, Y., & Zhang, Y. (2023) · Ibrain · doi:10.1002/ibra.12121 · Cited by 16
Zhou, L., & Simonian, A. L. (2024) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-081723-013033 · Cited by 18
Verma, S. S., Sen, C. K., Srivastava, R., Gnyawali, S. C., Katiyar, P., Sahi, A. K., Kumar, M., Rustagi, Y., Liu, S., Pandey, D., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.01.034 · Cited by 15
Active fusions of Cas9 orthologs
Josipović, G., Zoldoš, V., & Vojta, A. (2019) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2019.05.306 · Cited by 15
Kızılaslan, M., Arzık, Y., Çınar, M. U., & Konca, Y. (2021) · Annals of Animal Science · doi:10.2478/aoas-2021-0057 · Cited by 15
Harnessing natural DNA modifying activities for editing of the genome and epigenome
DeNizio, J. E., Schutsky, E. K., Berríos, K. N., Liu, M. Y., & Kohli, R. M. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.01.016 · Cited by 15
Epigenome‐wide association studies in Alzheimer’s disease; achievements and challenges
van den Hove, D., Riemens, R. J. M., Koulousakis, P., & Pishva, E. (2020) · Brain Pathology · doi:10.1111/bpa.12880 · Cited by 17
Comparative epigenetics in animal physiology: An emerging frontier
Navarro‐Martín, L., Martyniuk, C. J., & Mennigen, J. A. (2020) · Comparative Biochemistry and Physiology Part D Genomics and Proteomics · doi:10.1016/j.cbd.2020.100745 · Cited by 17
Dailey, K. M., Allgood, J. E., Johnson, P. R., Ostlie, M. A., Schaner, K., Brooks, B. D., & Brooks, A. E. (2021) · Future Microbiology · doi:10.2217/fmb-2020-0245 · Cited by 15
Alkhammash, A., & Alotaibi, G. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177853 · Cited by 15
Chen, Z. J. (2025) · The Plant Genome · doi:10.1002/tpg2.70064 · Cited by 13
“For example, one may use the genome-editing technology with neotype CRISPR/dCas9 to methylate or demethylate (X. S. Liu et al., 2016; Vojta et al., 2016) specific genomic features to alter chromatin states of epialleles in animal cells for epigenetic engineering.”
Imm, J. L., Kerrigan, T. L., Jeffries, A. R., & Lunnon, K. (2017) · Epigenomics · doi:10.2217/epi-2017-0076 · Cited by 14
Role of the CRISPR system in controlling gene transcription and monitoring cell fate (Review)
Baliou, S., Adamaki, M., Kyriakopoulos, A. M., Spandidos, D. A., Panayiotidis, M. I., Christodoulou, I., & Zoumpourlis, V. C. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.8099 · Cited by 14
“By contrast, the fusion of dCas9 to other epigenetic modulators, such as TET1 demethylase (56), LSD1 histone demethylase or the p300 histone acetyltransferase (57) seems to upregulate endogenous genes.”
Prader-Willi Syndrome: Molecular Mechanism and Epigenetic Therapy
Zhong, M., Chao, Y.-Q., & Zou, C. (2020) · Current Gene Therapy · doi:10.2174/1566523220666200424085336 · Cited by 14
Smith, A. R., Wheildon, G., & Lunnon, K. (2020) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12650 · Cited by 14
Martella, A., & Fisher, D. I. (2021) · The CRISPR Journal · doi:10.1089/crispr.2020.0108 · Cited by 14
“48,53 In this study, Choudhury et al . used dCas9–TET1 to target the BRCA1 promoter and re-activate gene expression selectively (Fig.”
Harnessing male germline epigenomics for the genetic improvement in cattle
Wang, X. Q., Li, W., Feng, X., Li, J., Liu, G. E., Fang, L., & Yu, Y. (2023) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-023-00874-9 · Cited by 15
Leitão, A. L., Costa, M. C., & Enguita, F. J. (2016) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2016.11.009 · Cited by 14
CRISPR-engineered genome editing for the next generation neurological disease modeling
Feng, W., Liu, H., & Kawauchi, D. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.05.019 · Cited by 15
“For instance, a recent study demonstrated that demethylation of promoter IV of Bdnf gene via sgRNA/dCas9-Tet1 in primary mouse neurons is sufficient to activate Bdnf expression in a scope similar to the induction of KCl mediated neuronal activity [76].”
The epigenomics of schizophrenia, in the mouse
Javidfar, B., Park, R., Kassim, B. S., Bicks, L. K., & Akbarian, S. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32566 · Cited by 14
Functional Genomics for Cancer Research: Applications In Vivo and In Vitro
O’Loughlin, T. A., & Gilbert, L. A. (2018) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030518-055742 · Cited by 14
“…perturbations, including single-base alterations or writable and rewritable epigenetic modifications (Gaudelli et al. 2017, Hess et al. 2016, Hilton et al. 2015, Hu et al. 2018, Komor et al. 2016, X.S. Liu et al. 2016, www.annualreviews.org • Functional Genomics for Cancer Research 355 A nn u.”
BackgroundInfluentialTailored chromatin modulation to promote tissue regeneration
Martínez‐Redondo, P., & Belmonte, J. C. I. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.04.015 · Cited by 14
Harnessing targeted DNA methylation and demethylation using dCas9
Pflueger, C., Swain, T., & Lister, R. (2019) · Essays in Biochemistry · doi:10.1042/ebc20190029 · Cited by 18
Applications of Functional Genomics for Drug Discovery
Kabadi, A. M., McDonnell, E., Frank, C. L., & Drowley, L. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220902092 · Cited by 15
The epigenome editors: How tools such as CRISPR offer new details about epigenetics
Willyard, C. (2017) · Nature Medicine · doi:10.1038/nm0817-900 · Cited by 13
Blum, K., Bowirrat, A., Baron, D., Elman, I., Makale, M. T., Cadet, J. L., Thanos, P. K., Hanna, C., Ahmed, R., Gondre-Lewis, M. C., et al. (2024) · Gene & Protein in Disease · doi:10.36922/gpd.1966 · Cited by 14
“160,161 They also encompass proteins involved in regulating histone PTMs such as NF κ B subunit p65 (which recruits HATs to acetylate core histones).”
BackgroundYang, Y.-M., Ding, Y.-F., Hu, Y.-Y., Fan, F., & Zhao, J.-L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1723270 · Cited by 14
“CRISPR-Cas9 technology may further be employed to knockout proliferation-related genes such as c-MYC (78, 79) or to restrict their division cycles through epigenetic editing (80, 81).”
Li, S., Hu, G., Chen, Y., Sang, Y., Tang, Q., & Liu, R. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03459-2 · Cited by 15
“…the regulatory effect of promoter DNA methylation on TERT expression, we used a genomic locus-specific DNA methylation editing system based on fusion of catalytically inactive Cas9 (dCAS9) with the catalytic domain of TET1 enzyme [34] to precisely edit the CpG methylation in TERT promoter (Fig.”
MethodGenetic therapies and potential therapeutic applications of CRISPR activators in the eye
Ng, B., Kaukonen, M. K., McClements, M. E., Shamsnajafabadi, H., MacLaren, R. E., & Cehajic‐Kapetanovic, J. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101289 · Cited by 13
Analog epigenetic memory revealed by targeted chromatin editing
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“Then, the normalized input u R 1 in the ODE model (3) can be written as 7) in which we define ~ u R 1 Finally, TET1 is an enzyme that catalyzes the conversion of DNA methylation into modifications that are not recognized by the maintenance enzyme DNMT1, and hence are passively removed through dilution.”
InfluentialAir pollution and the epigenome: A model relationship for the exploration of toxicoepigenetics
McCullough, S. D., Dhingra, R., Fortin, M. C., & Díaz-Sánchez, D. (2017) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2017.07.001 · Cited by 12
Optogenetics in cancer drug discovery
Kiełbus, M., Czapiński, J., Odrzywolski, A., Stasiak, G., Szymanska, K., Kałafut, J., Kos, M., Giannopoulos, K., Stepulak, A., & Rivero‐Müller, A. (2018) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2018.1437138 · Cited by 13
“mouse fibroblasts into myoblasts or inactive to active neurons [62].”
BackgroundGene editing in the context of an increasingly complex genome
Blighe, K., DeDionisio, L., Christie, K. A., Chawes, B., Shareef, S., Kakouli‐Duarte, T., Chao-Shern, C., Harding, V., Kelly, R. S., Castellano, L., et al. (2018) · BMC Genomics · doi:10.1186/s12864-018-4963-8 · Cited by 13
Mammalian haploid stem cells: establishment, engineering and applications
He, W., Chen, J., & Gao, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03069-6 · Cited by 11
CRISPR/Cas-Mediated Abiotic Stress Tolerance in Crops
Ahmad, A., Ashraf, S., Munawar, N., Jamil, A., Ghaffar, A., & Shahbaz, M. (2021) · Springer eBooks · doi:10.1007/978-981-15-7142-8_6 · Cited by 13
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Nuclear Architecture in the Nervous System: Development, Function, and Neurodevelopmental Diseases
Ito, K., & Takizawa, T. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00308 · Cited by 13
Patho- und Therapieepigenetik psychischer Erkrankungen
Ziegler, C., Schiele, M. A., & Domschke, K. (2018) · Der Nervenarzt · doi:10.1007/s00115-018-0625-y · Cited by 14
Genetic and epigenetic editing in nervous system
Day, J. J. (2019) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2019.21.4/jday · Cited by 13
Borkowska, J., Domaszewska-Szostek, A., Kołodziej, P., Wicik, Z., Połosak, J., Buyanovskaya, O. A., Charzewski, Ł., Stańczyk, M., Noszczyk, B. H., & Puzianowska‐Kuźnicka, M. (2020) · Epigenomics · doi:10.2217/epi-2019-0131 · Cited by 14
Epigenomic technologies for precision oncology
Weichenhan, D., Lipka, D. B., Lutsik, P., Goyal, A., & Plass, C. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.08.004 · Cited by 15
Lu, K., Liu, C., Liu, Y., Luo, A., Chen, J., Lei, Z., Kong, J., Xiao, X., Zhang, S., Wang, Y., et al. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00014 · Cited by 13
Conservation of Aging and Cancer Epigenetic Signatures across Human and Mouse
Pérez, R. F., Tejedor, J. R., Santamarina‐Ojeda, P., López, V., Urdinguio, R. G., Villamañán, L., Candiota, A. P., Vidal, N., Barradas, M., Fernández-Marcos, P. J., et al. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab112 · Cited by 13
“the development of targeted epigenetic editing tools (Liu et al. 2016), combined with the knowledge of epigenetic conservation in mouse and human, may serve as a powerful tool to explore the overall impact of both epigenetic and pathway alterations in multiple biological scenarios.”
BackgroundAnalog epigenetic memory revealed by targeted chromatin editing
Palacios, S., Bruno, S., Weiss, R., Salibi, E., Kane, A., Ilia, K., & Del Vecchio, D. (2024) · doi:10.1101/2024.02.13.580200 · Cited by 13
Horii, T., Morita, S., Kimura, M., & Hatada, I. (2022) · Epigenetics & Chromatin · doi:10.1186/s13072-022-00474-3 · Cited by 12
In vivo DNA methylation editing in zebrafish
Liang, F., Dong, Z., Ye, J., Hu, W., Bhandari, R. K., Mai, K., & Wang, X. (2023) · Epigenetics · doi:10.1080/15592294.2023.2192326 · Cited by 14
“The dCas9-Dnmt7CD and dCas9-Tet2CD fusion proteins were constructed by adding the Dnmt7 or Tet2 catalytic domain to the C-terminus of the inactive Cas9 (dCas9) via a short Gly4Ser linker (Figure 1a) [5,6,11].”
Unexplored power of CRISPR-Cas9 in neuroscience, a multi-OMICs review
Banazadeh, M., Abiri, A., Poortaheri, M. M., Asnaashari, L., Langarizadeh, M. A., & Forootanfar, H. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130413 · Cited by 12
Targeting neuronal epigenomes for brain rejuvenation
Zocher, S. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00148-8 · Cited by 13
“In recent years, tools for the locus-speci fi c editing of epigenetic patterns based on the CRISPR/Cas9 system have been developed (Hilton et al, 2015; Kearns et al, 2015; Liu et al, 2016; Kwon et al, 2017; Liu and Jaenisch, 2019).”
BackgroundMethodInfluentialNon-viral Methodology for Efficient Co-transfection
Kretzmann, J. A., Evans, C. W., Nörret, M., Blancafort, P., & Iyer, K. S. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7774-1_13 · Cited by 12
Assessing the epigenetic risks of assisted reproductive technologies: a way forward
Zacchini, F., Sampino, S., Stankiewicz, A. M., Haaf, T., & Ptak, G. (2019) · The International Journal of Developmental Biology · doi:10.1387/ijdb.180402gp · Cited by 12
“Emerging technologies for editing DNA methylation patterns (Liu et al., 2016) will be essential for providing a functional proof of the epigenetic mechanism underlying ART-associated disease risks.”
BackgroundThomas, R. J., Trapani, D., Sait, L. G., Tomková, M., Fernández–Rozadilla, C., Sahnane, N., Woolley, C. E., Belnoue-Davis, H. L., Chegwidden, L., Kriaučionis, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-49952-x · Cited by 12
Ślaska‐Kiss, K., Zsibrita, N., Koncz, M., Albert, P., Csábrádi, Á., Szentes, S., & Kiss, A. (2021) · Scientific Reports · doi:10.1038/s41598-021-94528-3 · Cited by 12
Tack, L. J. W., van der Straaten, S., Riedl, S., Springer, A., Holterhus, P., Hornig, N., Kolesińska, Z., Niedziela, M., Baronio, F., Balsamo, A., et al. (2021) · Clinical Endocrinology · doi:10.1111/cen.14614 · Cited by 14
“Highly innovative in vitro and animal studies, for example based on DNA methylation editing are required to explore this hypothesis.(26) Another theory how placental insufficiency could be linked to atypical sex development is that masculinization of the foetus is not only dependent on testosterone secreted by the tes…”
BackgroundEpigenetic Editing in Prostate Cancer: Challenges and Opportunities
Pacheco, M. B., Camilo, V., Henrique, R., & Jerónimo, C. (2021) · Epigenetics · doi:10.1080/15592294.2021.1939477 · Cited by 12
“Nonetheless, the expression levels of these editing domains influence the potency and duration of epigenetic editing [48,66,95,104].”
BackgroundMethodThe potential role of DNA methylation as preventive treatment target of epileptogenesis
Berger, T. C., Taubøll, E., & Heuser, K. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.931356 · Cited by 12
Megagiannis, P., Suresh, R., Rouleau, G. A., & Zhou, Y. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114562 · Cited by 12
Sohrabi, M., Babaei, Z., Haghpanah, V., Larijani, B. A., Abbasi, A. A., & Mahdavi, M. R. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113872 · Cited by 12
Liu, Y., Ding, D., Liu, H., & Sun, X. S. (2017) · Biology of Reproduction · doi:10.1093/biolre/iox028 · Cited by 12
“achieved epigenetic edit by fusion of Tet1 or Dnmt3a with a catalytically inactive Cas9 (dCas9) and altered gene expression in the neighboring loop by targeted de novo 415 methylation of a CTCF loop anchor site [86].”
BackgroundCancer induction and suppression with transcriptional control and epigenome editing technologies
Nakade, S., Yamamoto, T., & Sakuma, T. (2017) · Journal of Human Genetics · doi:10.1038/s10038-017-0377-8 · Cited by 11
Programmable sequential mutagenesis by inducible Cpf1 crRNA array inversion
Chow, R. D.-W., Kim, H. R., & Chen, S. (2018) · Nature Communications · doi:10.1038/s41467-018-04158-z · Cited by 12
How Crisp is CRISPR? CRISPR-Cas-mediated crop improvement with special focus on nutritional traits
Kaul, T., Sony, S. K., Raman, N. M., Eswaran, M., Verma, R., Prakash, A. T., Bharti, J., Motelb, K. F. A., & Kaul, R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818581-0.00011-5 · Cited by 12
Chen, A. C. H., Huang, W. M., Fong, S. W., Chan, C. C.-S., Lee, K. C., Yeung, W. S. B., & Lee, Y. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910729 · Cited by 12
A Practical Guide to Genome Editing Using Targeted Nuclease Technologies
Porter, S. N., Levine, R. M., & Pruett‐Miller, S. M. (2019) · Comprehensive physiology · doi:10.1002/cphy.c180022 · Cited by 18
“Demethylation of differentially methylated regions upstream of Myod1 in mouse embryonic fibroblasts (MEFs) using dCas9-TET1 in combination with DNA methyltransferase treatment led to upregulated expression of Myod1 and induced myotube formation (256).”
Szukowska, A., Żuk, M., Sztompke, J., Bednarz, B., & Kaźmierczak, U. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110524 · Cited by 10
“An important advantage of induced epigenetic changes is their heritability across generations, making ASO-based technologies an attractive alternative to classical genetic modification methods [40].”
Editing DNA methylation in vivo
Pan, R. J., Ren, J., Chen, X., Flores, L. F., Gonzalez, R. V. L., Adonnino, A. A., Lofts, B. R., Waldo, J. J., Halmai, J. A. N. M., Devinsky, O., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67222-5 · Cited by 11
“For cell culture experiments, sgRNAs were cloned into the pgRNA back-bone (Addgene 84477) 11 using an AarIcut site.”
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Gong, L., Liu, X., Wu, J., & He, M. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01292-x · Cited by 8
Self-citationDNA methylation–independent long-term epigenetic silencing with dCRISPR/Cas9 fusion proteins
Ding, L., Schmitt, L. T., Brux, M., Sürün, D., Augsburg, M., Lansing, F., Mircetic, J., Theis, M., & Buchholz, F. (2022) · Life Science Alliance · doi:10.26508/lsa.202101321 · Cited by 16
“DNA methylation at promoters has been associated with persistent transcriptional repression (Amabile et al, 2016; Liu et al, 2016; Nuñez et al, 2021).”
BackgroundNickel-induced alterations to chromatin structure and function
Gaspar, A. D., & Cuddapah, S. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116317 · Cited by 11
3D genome alterations and editing in pathology
Tiukacheva, E. A., Ulianov, S. V., Karpukhina, A. A., Razin, S. V., & Vassetzky, Y. S. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.02.005 · Cited by 14
Burenkova, O. V., & Grigorenko, E. L. (2024) · Developmental Psychobiology · doi:10.1002/dev.22479 · Cited by 11
From womb to wellness: early environmental exposures, cord blood DNA methylation and disease origins
Mirzakhani, H. (2024) · Epigenomics · doi:10.1080/17501911.2024.2390823 · Cited by 13
Wang, Q., Chen, M., Yang, B. J., Zheng, W., Liu, X., & Jian, G. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113766 · Cited by 14
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CRISPR-Cas Systems: A Functional Perspective and Innovations
Navarro, C., Diaz, M. P., Durán, P., Castro, A., Díaz, A., Cano, C., Carbonell, A., Solano-Jimenez, D.-S., Rivera-Porras, D., Contreras-Velásquez, J., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083645 · Cited by 16
“Current research focuses on optimising methyltransferase combinations to enhance specificity and reduce off-target effects [177].”
DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities
Deshmukh, M. G., Brooks, V. T., Roy, S. F., Milette, S., Bosenberg, M., & Micevic, G. (2025) · Clinical Epigenetics · doi:10.1186/s13148-025-01865-5 · Cited by 15
“…of DNA dem-ethylase Ten-Eleven Translocation (TET) dioxygenase1 (TET1) or DNMT3 with catalytically inactive Cas9 enables targeted DNA methylation editing of methylated or unmethylated promoter sequences leading to activation or silencing, respectively, of the associated endogenous reporter [101].”
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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