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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InfluentialModel-based Analysis of ChIP-Seq (MACS)
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InfluentialMultiplex Genome Engineering Using CRISPR/Cas Systems
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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).”
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×
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DNA methylation patterns and epigenetic memory
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“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
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Functional methylome analysis of human diabetic kidney disease
Park, J., Guan, Y., Sheng, X., Gluck, C. A., Seasock, M. J., Hakimi, A. A., Qiu, C., Pullman, J. M., Verma, A. K., Li, H., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.128886 · Cited by 74
Engineered tissues and strategies to overcome challenges in drug development
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Self-citationRole of Epigenomics in Bone and Cartilage Disease
van Meurs, J. B. J., Boer, C. G., López-Delgado, L., & Riancho, J. A. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3662 · Cited by 75
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Synthetic lethal strategies for the development of cancer therapeutics
Ngoi, N. Y. L., Gallo, D., Torrado, C., Nardo, M., Durocher, D., & Yap, T. A. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00966-z · Cited by 81
Epigenetic inheritance and intergenerational effects in mollusks
Fallet, M., Luquet, É., David, P., & Cosseau, C. (2019) · Gene · doi:10.1016/j.gene.2019.144166 · Cited by 75
CRISPR-Based Epigenome Editing: Mechanisms and Applications
Fadul, S. M., Arshad, A., & Mehmood, R. (2023) · Epigenomics · doi:10.2217/epi-2023-0281 · Cited by 80
Epigenomes in Cardiovascular Disease
Rosa‐Garrido, M., Chapski, D. J., & Vondriska, T. M. (2018) · Circulation Research · doi:10.1161/circresaha.118.311597 · Cited by 73
“…DNMT3a or Tet1 and combined with guide RNAs to localize the complex, can induce altered DNA methylation of specific loci in somatic cells in vivo commensurate with desired changes in gene expression 231 (techniques for remodeling chromatin loops with designer CRISPR tools have also emerged 232 ).”
A CRISPR Interference Platform for Efficient Genetic Repression in Candida albicans
Wensing, L. F., Sharma, J., Uthayakumar, D., Proteau, Y., Chavez, A., & Shapiro, R. S. (2019) · mSphere · doi:10.1128/msphere.00002-19 · Cited by 71
“Since their development as genetic editing technologies (39), CRISPR systems have been further modified to achieve alternative outcomes, such as base-editing (40–42), RNA editing (43), epigenetic modifications (44, 45), and transcriptional regulation (46).”
BackgroundCRISPR-based metabolic pathway engineering
Zhao, D., Zhu, X., Zhou, H., Sun, N., Wang, T., Bi, C., & Zhang, X. (2020) · Metabolic Engineering · doi:10.1016/j.ymben.2020.10.004 · Cited by 70
Stenzig, J., Schneeberger, Y., Löser, A., Peters, B. S., Schaefer, A., Zhao, R., Ng, S. L., Höppner, G., Geertz, B., Hirt, M. N., et al. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.05.012 · Cited by 71
Plant synthetic biology could drive a revolution in biofuels and medicine
Mortimer, J. C. (2018) · Experimental Biology and Medicine · doi:10.1177/1535370218793890 · Cited by 70
“CRISPR-based systems in particular are expanding rapidly, with new functions added via gene-fusion with the endonuclease, such as gene repression(30) and, as has been shown in mammalian cells, epigenetic modification.(31)”
BackgroundA high‐throughput transient expression system for rice
Page, M. T., Parry, M. A. J., & Carmo‐Silva, E. (2019) · Plant Cell & Environment · doi:10.1111/pce.13542 · Cited by 72
“Additionally, the platform presented here could be used to screen the efficacy of gRNAs in CRISPR/Cas9 genome editing or even assess more recent advancements in CRISPR/Cas9 technology such as DNA methylation editing or base editing (Gaudelli et al., 2017; Liu et al., 2016).”
MethodEpigenetic genes and epilepsy — emerging mechanisms and clinical applications
Van Loo, K. M. J., Carvill, G. L., Becker, A. J., Conboy, K., Goldman, A. M., Kobow, K., Lopes-Cendes, I., Reid, C. A., van Vliet, E. A., & Henshall, D. C. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00693-y · Cited by 68
APOBEC: From mutator to editor
Yang, B., Li, X., Lei, L., & Chen, J. (2017) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2017.04.009 · Cited by 70
What has single-cell RNA-seq taught us about mammalian spermatogenesis?
Suzuki, S., Diaz, V. D., & Hermann, B. P. (2019) · Biology of Reproduction · doi:10.1093/biolre/ioz088 · Cited by 70
High-Throughput Approaches to Pinpoint Function within the Noncoding Genome
Montalbano, A., Canver, M. C., & Sanjana, N. E. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.017 · Cited by 68
“(F) dCas9 fused to DNA methylases (e.g., DNMT3A) (Lei et al., 2017; Liu et al., 2016; Vojta et al., 2016) or demethylases (TET1) (Liu et al., 2016) introduces or removes methyl groups at CpG dinucleotides (silencing of gene expression), respectively.”
InfluentialSadiković, B., Aref‐Eshghi, E., Levy, M. A., & Rodenhiser, D. I. (2019) · Epigenomics · doi:10.2217/epi-2018-0192 · Cited by 68
Gene editing and its applications in biomedicine
Li, G., Li, X., Zhuang, S., Wang, L., Zhu, Y., Chen, Y., Sun, W. C., Wu, Z., Zhou, Z. L., Chen, J., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-021-2057-0 · Cited by 66
“screens have identified coding genes that modify cell growth and confer cancer therapeutic resistance (Joung et al., 2017; Liu et al., 2016).”
BackgroundMethodInfluentialThe impact of DNA methylation on CTCF-mediated 3D genome organization
Monteagudo, A., Noordermeer, D., & Greenberg, M. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01241-6 · Cited by 70
“Such tools have already been used at CTCF-binding sites 108,109 and provide an avenue to dissect novel loci uncovered from aforementioned genome-wide approaches.”
Causal role of histone acetylations in enhancer function
Pradeepa, M. M. (2016) · Transcription · doi:10.1080/21541264.2016.1253529 · Cited by 69
Gene-Specific Targeting of DNA Methylation in the Mammalian Genome
Urbano, A., Smith, J., Weeks, R. J., & Chatterjee, A. (2019) · Cancers · doi:10.3390/cancers11101515 · Cited by 67
Ge, S., Lin, S., Zhao, Z., & Sun, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.17479 · Cited by 68
“Satisfyingly, the epigenetic editing system has represented a powerful toolbox that can be used to drastically modify the epigenetic landscape of a specific regulatory element, and this useful technique may be readily adopted in gene and cell therapies [105, 106].”
MethodDNA-Methylation: Master or Slave of Neural Fate Decisions?
Stricker, S. H., & Götz, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00005 · Cited by 66
“So far, Tet1 and Dnmt3a have been used most prominently to show that DNA methylation on the accurate locus can indeed influence transcription of a gene close by (Amabile et al., 2016; Choudhury et al., 2016; Liu et al., 2016; Xu et al., 2016).”
BackgroundNagu, P., Parashar, A., Behl, T., & Mehta, V. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01829-3 · Cited by 68
“The majority of methylation reactions on mammalian DNA occur with the cytosine residue; however, in recent times the methylation of adenine bases has also been detected (Liu et al. 2016).”
BackgroundThe use of new CRISPR tools in cardiovascular research and medicine
Nishiga, M., Liu, C., Qi, L. S., & Wu, J. C. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00669-3 · Cited by 71
Han, F., Liu, W., Shi, X., Yang, J., Zhang, X., Li, Z., JIANG, X. H., Li, Y., Li, J., Huang, C., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.04.026 · Cited by 66
Epigenetic regulation in cell senescence
Cheng, L.-Q., Zhang, Z.-Q., Chen, H.-Z., & Liu, D.-P. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1581-x · Cited by 64
Developmental Epigenetics: Phenotype and the Flexible Epigenome
John, R. M., & Rougeulle, C. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00130 · Cited by 68
“In this respect, epiediting holds great promise (Liu et al., 2016; Thakore et al., 2016).”
BackgroundGenome-wide CRISPR-Cas9 screening in mammalian cells
Yu, J., & Yusa, K. (2019) · Methods · doi:10.1016/j.ymeth.2019.04.015 · Cited by 66
DNA methylation and de-methylation using hybrid site-targeting proteins
Lei, Y., Huang, Y., & Goodell, M. A. (2018) · Genome biology · doi:10.1186/s13059-018-1566-2 · Cited by 67
CRISPR-Based Synthetic Transcription Factors In Vivo: The Future of Therapeutic Cellular Programming
Pandelakis, M., Delgado, E., & Ebrahimkhani, M. R. (2020) · Cell Systems · doi:10.1016/j.cels.2019.10.003 · Cited by 63
Multigenerational epigenetic inheritance: One step forward, two generations back
Tuscher, J. J., & Day, J. J. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104591 · Cited by 63
Josipović, G., Tadić, V., Klasić, M., Zanki, V., Bečeheli, I., Chung, F. F., Ghantous, A., Keser, T., Madunić, J., Bošković, M., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz709 · Cited by 68
Engineering of Effector Domains for Targeted DNA Methylation with Reduced Off-Target Effects
Hofacker, D. T., Broche, J., Laistner, L., Adam, S., Bashtrykov, P., & Jeltsch, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020502 · Cited by 62
Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option?
Mirgayazova, R., Khadiullina, R., Chasov, V. V., Mingaleeva, R. N., Рифкатовна, М. Р., Rizvanov, A. A., & Bulatov, E. (2020) · Genes · doi:10.3390/genes11060704 · Cited by 68
“Abbreviations AACR—American Association for Cancer Research; ABE—adenine base editor; BE—base editor; CAR-T— chimeric antigen receptor T cell; Cas—CRISPR-associated; CBE—cytosine base editor; CCS—computational CRISPR strategy; CER—critical enhancer region; CGI—CpG island; CRISPR/Cas—clustered regularly interspaced sho…”
BackgroundInfluentialCao, L., Wang, S., Zhang, Y., Wong, K., Nakatsu, G., Wang, X., Wong, S. H., Ji, J., & Yu, J. Q. (2018) · Oncogene · doi:10.1038/s41388-018-0220-5 · Cited by 64
“Once the functional CpG sites are validated, the CRISPR/Cas9 based DNA methylation editing tool can be applied to predictably alter the epigenetic state-of-target sequences [34], thereby fostering the development of targeted cancer therapy.”
MethodTET-mediated epimutagenesis of the Arabidopsis thaliana methylome
Ji, L., Jordan, W. T., Shi, X., Hu, L., He, C., & Schmitz, R. J. (2018) · Nature Communications · doi:10.1038/s41467-018-03289-7 · Cited by 60
Quantitative Epigenetics: A New Avenue for Crop Improvement
Gahlaut, V., Zinta, G., Jaiswal, V., & Kumar, S. (2020) · Epigenomes · doi:10.3390/epigenomes4040025 · Cited by 61
Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine
Basu, A., & Tiwari, V. K. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01131-4 · Cited by 61
Johnston, A. D., Simões‐Pires, C. A., Thompson, T. V., Suzuki, M., & Greally, J. M. (2019) · Nature Communications · doi:10.1038/s41467-019-11412-5 · Cited by 63
Toward the Development of Epigenome Editing-Based Therapeutics: Potentials and Challenges
Ueda, J., Yamazaki, T., & Funakoshi, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054778 · Cited by 60
Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation
Wang, S., Zha, L., Cui, X., Yeh, Y., Liu, R., Jing, J., Shi, H., Chen, W., Hanover, J. A., Yin, J., et al. (2023) · Advanced Science · doi:10.1002/advs.202206068 · Cited by 63
Liu, A., Wu, Q., Peng, D., Arés, I., Anadón, A., López-Torres, B., Martínez‐Larrañaga, M., Wang, X., & Martínez, M. (2020) · Medicinal Research Reviews · doi:10.1002/med.21696 · Cited by 59
Enhancer-gene specificity in development and disease
Pachano, T., Haro, E., & Rada-Iglesias, Á. (2022) · Development · doi:10.1242/dev.186536 · Cited by 57
Schlosberg, C., VanderKraats, N. D., & Edwards, J. R. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx078 · Cited by 52
CRISPR-Mediated Reactivation of DKK3 Expression Attenuates TGF-β Signaling in Prostate Cancer
Kardooni, H., González‐Gualda, E., Stylianakis, E., Saffaran, S., Waxman, J., & Kypta, R. M. (2018) · Cancers · doi:10.3390/cancers10060165 · Cited by 59
“In order to determine if DKK3 expression could be induced by targeted demethylation of the DKK3 promoter, we used an expression vector encoding dCas9 fused to the catalytic domain of the demethylase Tet1 (dCas9-Tet1CD) [42].”
BackgroundMethodCramer, T., Rosenberg, T., Kisliouk, T., & Meiri, N. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0280-5 · Cited by 60
Imkeller, K., Ambrosi, G., Boutros, M., & Huber, W. K. (2020) · Genome biology · doi:10.1186/s13059-020-1939-1 · Cited by 58
Engineering 3D genome organization
Wang, H., Han, M., & Qi, L. S. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00325-5 · Cited by 62
Editing the Epigenome to Tackle Brain Disorders
Liu, X. S., & Jaenisch, R. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.10.003 · Cited by 56
“DNA methylation in the mammalian genome [16,17].”
BackgroundSelf-citationEpigenome editing for targeted DNA (de)methylation: a new perspective in modulating gene expression
Seem, K., Kaur, S., Kumar, S., & Mohapatra, T. (2024) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2024.2320659 · Cited by 59
“…regulatory element (p300, lSD1, DNMt3A, tet1) was reported to strongly activate the expression of the gene (Hilton et al. 2015; Kearns et al. 2015; liu et al. 2016; choudhury et al. 2016; Saunderson et al. 2017). to improve flexibility for the target sequence, gRNA fused with RNA aptamer (MS2 and…”
BackgroundGenome Engineering for Personalized Arthritis Therapeutics
Adkar, S. S., Brunger, J. M., Willard, V. P., Wu, C., Gersbach, C. A., & Guilak, F. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.002 · Cited by 57
“[72] Likewise, DNA modifications can be specifically altered with DNMT3a methyltransferase.[73] These gene activators and repressors might have therapeutic potential for arthritic joints by targeting epigenetic modifications in both inflammatory cells and resident cell types, although this remains largely unexplored.”
Marx, N., Grünwald‐Gruber, C., Bydlinski, N., Dhiman, H., Ly, N. N., Klanert, G., & Borth, N. (2018) · Biotechnology Journal · doi:10.1002/biot.201700217 · Cited by 57
CRISPR-based gene expression control for synthetic gene circuits
Santos‐Moreno, J., & Schaerli, Y. (2020) · Biochemical Society Transactions · doi:10.1042/bst20200020 · Cited by 59
Singh, K., Rustagi, Y., Abouhashem, A. S., Tabasum, S., Verma, P., Hernandez, E., Pal, D., Khona, D. K., Mohanty, S. K., Kumar, M., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci157279 · Cited by 57
“A TNT-based topical 402 CRISPR/dCas9 system was thus employed wherein the goal was to generate chimeric versions of 403 dCas9 fused with TET to achieve targeted TP53 demethylation (92).”
A translational perspective on epigenetics in allergic diseases
Tost, J. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.07.009 · Cited by 57
CRISPR-Based Tools in Immunity
Simeonov, D. R., & Marson, A. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041522 · Cited by 57
Targeted Reactivation of FMR1 Transcription in Fragile X Syndrome Embryonic Stem Cells
Haenfler, J. M., Skariah, G., Rodriguez, C. M., da Rocha, A. M., Parent, J. M., Smith, G. D., & Todd, P. K. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00282 · Cited by 59
Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome
Horii, T., Morita, S., Hino, S., Kimura, M., Hino, Y., Kogo, H., Nakao, M., & Hatada, I. (2020) · Genome biology · doi:10.1186/s13059-020-01991-8 · Cited by 61
Li, J., Xiao, L., Yan, N., Li, Y., Wang, Y., Qin, X., Zhao, D., Liu, M., Li, N., & Lin, Y. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202104141 · Cited by 57
Epigenetic editing: Dissecting chromatin function in context
Policarpi, C., Dabin, J., & Hackett, J. A. (2021) · BioEssays · doi:10.1002/bies.202000316 · Cited by 54
DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice
McGrath‐Morrow, S. A., Ndeh, R., Helmin, K. A., Chen, S.-Y., Anekalla, K. R., Abdala‐Valencia, H., D’Alessio, F. R., Collaco, J. M., & Singer, B. D. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003589 · Cited by 55
“Future studies exploiting novel CRISPR-based DNA methylation– editing systems could elucidate causal proof of these associations (38).”
BackgroundMethods and applications of CRISPR/Cas system for genome editing in stem cells
Yang, G., & Huang, X. (2019) · Cell Regeneration · doi:10.1016/j.cr.2019.08.001 · Cited by 55
“Apart from transcriptional effectors, DNA methyltransferase such as DNMT3a and DNMT3b can also be fused to dCas9 to enable targeted methylation or demethylation, which is critical for in situ epigenetic engineering and epigenetic studies [15,43].”
BackgroundCRISPR/Cas mediated epigenome editing for cancer therapy
Ansari, I., Chaturvedi, A., Chitkara, D., & Singh, S. P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.018 · Cited by 58
Repurposing type I–F CRISPR–Cas system as a transcriptional activation tool in human cells
Chen, Y., Liu, J., Zhi, S., Zheng, Q., Ma, W., Huang, J., Liu, Y., Liu, D., Liang, P., & Songyang, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-16880-8 · Cited by 54
Ghoshal, B., Vong, B., Picard, C. L., Feng, S., Tam, J. M., & Jacobsen, S. E. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008983 · Cited by 54
“Such CRISPR-dCAS9 81 based tools have been used to regulate gene expression and/or modify the epigenome 82 across multiple species [3, 6-9].”
MethodDynamic Regulation of DNA Methylation and Brain Functions
Xie, J., Xie, L., Wei, H., Li, X., & Li, L. (2023) · Biology · doi:10.3390/biology12020152 · Cited by 57
Noncoding RNAs as therapeutic targets in early stage diabetic kidney disease
Kato, M. V. (2018) · Kidney Research and Clinical Practice · doi:10.23876/j.krcp.2018.37.3.197 · Cited by 56
“More interestingly, using a fusion protein of Cas9 with DNA methyltransferase, histone modifying enzymes, or other DNA or histone modifying enzymes, it is possible to change the epigenetic marks, DNA methylation, histone acetylation, or methylation in the locus-specific manner [172-176].”
BackgroundMethylation of immune synapse genes modulates tumor immunogenicity
Berglund, A., Mills, M. N., Putney, R. M., Hamaidi, I., Mulé, J. J., & Kim, S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci131234 · Cited by 54
“Alternatively, targeted editing of tumor methylation of immune synapse genes by TET1 or DNMT3a via CRISPR may allow personalized approaches to augment immunotherapy (20).”
BackgroundCell Reprogramming With CRISPR/Cas9 Based Transcriptional Regulation Systems
Шакирова, К. М., Ovchinnikova, V. Y., & Dashinimaev, E. B. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00882 · Cited by 54
Rittiner, J. E., Moncalvo, M., Chiba‐Falek, O., & Kantor, B. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00148 · Cited by 53
“Furthermore, the dCas9-DNMT3A activity can be significantly increased by the additional fusion of the DNMT3A heterodimerization partner DNMT3L (Saunderson et al., 2017; Stepper et al., 2017).”
BackgroundMethodInfluentialVogt, G. (2021) · Journal of Biosciences · doi:10.1007/s12038-021-00138-6 · Cited by 56
“It can also be applied to add and remove individual methylation marks on the DNA (Liu et al. 2016; Xu et al. 2016).”
BackgroundTaghbalout, A., Du, M., Jillette, N., Rosikiewicz, W., Rath, A., Heinen, C. D., Li, S., & Cheng, A. W. (2019) · Nature Communications · doi:10.1038/s41467-019-12339-7 · Cited by 53
Locus-specific DNA methylation of Mecp2 promoter leads to autism-like phenotypes in mice
Lu, Z., Liu, Z., Mao, W., Wang, X., Zheng, X., Chen, S., Cao, B., Huang, S., Zhang, X., Zhou, T., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2290-x · Cited by 52
Roth, G. V., Gengaro, I. R., & Qi, L. S. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.07.007 · Cited by 59
Jin, M., de Loubresse, N. G., Kim, Y., Kim, J., & Yin, P. (2019) · ACS Synthetic Biology · doi:10.1021/acssynbio.9b00141 · Cited by 52
Artificial escape from XCI by DNA methylation editing of the CDKL5 gene
Halmai, J. A. N. M., Deng, P., Gonzalez, C. E., Halmai, N. B., Cameron, D. L., Carter, J., Buchanan, F. K. B., Waldo, J. J., Lock, S., Anderson, J. D., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1214 · Cited by 54
“While it was suggested that the effects of dCas9-TET1CD are specific (26), we and others demonstrate global DNA methylome changes (29).”
BackgroundDNA Methylation Editing by CRISPR-guided Excision of 5-Methylcytosine
Devesa-Guerra, I., Morales‐Ruíz, T., Pérez-Roldán, J., Parrilla-Doblas, J. T., León, M. D., García‐Ortiz, M. V., Ariza, R. R., & Roldán‐Arjona, T. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.02.007 · Cited by 51
Wang, J., Yang, J., Li, D., & Li, J. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188454 · Cited by 53
Epigenetics in formation, function, and failure of the endocrine pancreas
Golson, M. L., & Kaestner, K. H. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.05.015 · Cited by 52
Targeting cancer epigenetics with CRISPR-dCAS9: Principles and prospects
Rahman, M. M., & Tollefsbol, T. O. (2020) · Methods · doi:10.1016/j.ymeth.2020.04.006 · Cited by 51
Targeted DNA demethylation produces heritable epialleles in rice
Tang, S., Yang, C., Wang, D., Deng, X. M., Cao, X., & Song, X. (2021) · Science China Life Sciences · doi:10.1007/s11427-021-1974-7 · Cited by 51
DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line
Illum, L. R. H., Bak, S. T., Lund, S., & Nielsen, A. L. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0189 · Cited by 51
Ectopic targeting of CG DNA methylation in Arabidopsis with the bacterial SssI methyltransferase
Liu, W., Gallego‐Bartolomé, J., Zhou, Y., Zhong, Z., Wang, M., Wongpalee, S. P., Gardiner, J., Feng, S., Kuo, P. H., & Jacobsen, S. E. (2021) · Nature Communications · doi:10.1038/s41467-021-23346-y · Cited by 54
Suzuki, T., Maeda, S., Furuhata, E., Shimizu, Y., Nishimura, H., Kishima, M., & Suzuki, H. (2017) · Epigenetics & Chromatin · doi:10.1186/s13072-017-0169-6 · Cited by 47
Reversing Mechanoinductive DSP Expression by CRISPR/dCas9–mediated Epigenome Editing
Qu, J. T., Zhu, L., Zhou, Z., Chen, P., Liu, S., Locy, M. L., Thannickal, V. J., & Zhou, Y. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201711-2242oc · Cited by 51
In vivo epigenome editing and transcriptional modulation using CRISPR technology
Lau, C., & Suh, Y. (2018) · Transgenic Research · doi:10.1007/s11248-018-0096-8 · Cited by 51
Zhang, T., Zhao, F., Li, J., Sun, X., Zhang, X., Wang, H., Peng, F., Lai, L., Li, Z., & Sui, T. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae110 · Cited by 48
Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction.
Cribbs, A. P., & Perera, S. (2017) · PubMed · Cited by 49
Sequence-specific m6A demethylation in RNA by FTO fused to RCas9
Rau, K., Rösner, L., & Rentmeister, A. (2019) · RNA · doi:10.1261/rna.070706.119 · Cited by 49
Modeling the complex genetic architectures of brain disease
Fernando, M. B., Ahfeldt, T., & Brennand, K. (2020) · Nature Genetics · doi:10.1038/s41588-020-0596-3 · Cited by 48
Epigenome Remodeling in Cholangiocarcinoma
O’Rourke, C. J., Lafuente-Barquero, J. F., & Andersen, J. B. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.05.002 · Cited by 48
Gene therapy for cystic fibrosis: Challenges and prospects
Sui, H., Xu, X., Su, Y., Gong, Z., Yao, M., Liu, X., Zhang, T., Jiang, Z., Bai, T., Wang, J., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1015926 · Cited by 56
“When catalytically inactive Cas (dCas) is used, the complex binds to the target without creating strand breaks (Liu et al., 2016).”
MethodSelf-citationProgress and Perspective of CRISPR‐Cas9 Technology in Translational Medicine
Zheng, R., Zhang, L., Parvin, R., Su, L., Chi, J., Shi, K., Ye, F., & Huang, X. (2023) · Advanced Science · doi:10.1002/advs.202300195 · Cited by 56
Epigenome dysregulation in cholangiocarcinoma
O’Rourke, C. J., Muñoz-Garrido, P., Aguayo, E. L., & Andersen, J. B. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.06.014 · Cited by 48
“Rather, functional epigenetics experiments involving the targeted modulation of epimutations followed by their rescue are required, technologies which are only in the early stages of development [96-98].”
Jeffries, M. A. (2018) · Clinical Immunology · doi:10.1016/j.clim.2018.02.001 · Cited by 51
Inactivation of SMARCA2 by promoter hypermethylation drives lung cancer development
Wu, J., He, K., Zhang, Y., Song, J., Shi, Z., Chen, W., & Shao, Y. (2018) · Gene · doi:10.1016/j.gene.2018.11.032 · Cited by 48
Ford, E., Grimmer, M. R., Stolzenburg, S., Bogdanovic, O., Mendoza, A. D., Farnham, P. J., Blancafort, P., & Lister, R. (2017) · doi:10.1101/170506 · Cited by 45
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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