CRISPR/Cas9-Based Engineering of the Epigenome

Cell Stem Cell

Volumn 21, Issue 4, 2017, Pages 431-447

  Pulecio, Julian ^a,b,c   Verma, Nipun ^c,d   Mejía Ramírez, Eva ^a   Huangfu, Danwei ^c   Raya, Angel ^a,b,e  

^a HOSPITAL UNIVERSITARI DE BELLVITGE   (Spain)

^b BIOMATERIALES Y NANOMEDICINA CIBER BBN   (Spain)

^c MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^d Weill Cornell Medical Center   (United States)

^e INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

Author keywords

chromatin architecture; CRISPR dCas9; DNA methylation; histone modifications; targeted epigenome engineering; targeted gene edition; transcriptional regulation

Indexed keywords

UNTRANSLATED RNA;

CELL ENGINEERING; CHROMATIN; CRISPR-CAS9 SYSTEM; DEMETHYLATION; DNA METHYLATION; EPIGENETICS; EUKARYOTE; GENE AMPLIFICATION; GENE EXPRESSION; HISTONE MODIFICATION; HUMAN; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN MODIFICATION; REVIEW; SILENCER GENE; STEM CELL; STEM CELL SELF-RENEWAL; TRANSCRIPTION REGULATION; ANIMAL; CRISPR CAS SYSTEM; GENETIC EPIGENESIS; GENETICS; GENOME; METABOLISM; REGENERATIVE MEDICINE;

ANIMALS; CHROMATIN; CRISPR-CAS SYSTEMS; EPIGENESIS, GENETIC; GENOME; HUMANS; REGENERATIVE MEDICINE; STEM CELLS;

EID: 85032478389     PISSN: 19345909     EISSN: 18759777     Source Type: Journal    
DOI: 10.1016/j.stem.2017.09.006     Document Type: Review

References (194)

1. Adamo, A., Sesé, B., Boue, S., Castaño, J., Paramonov, I., Barrero, M.J., Izpisua Belmonte, J.C., LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat. Cell Biol. 13 (2011), 652–659.
2. Adamson, B., Norman, T.M., Jost, M., Cho, M.Y., Nunez, J.K., Chen, Y., Villalta, J.E., Gilbert, L.A., Horlbeck, M.A., Hein, M.Y., et al. A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Cell 167 (2016), 1867–1882.
3. Allis, C.D., Jenuwein, T., The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17 (2016), 487–500.
4. Allis, C.D., Jenuwein, T., Reinberg, D., Epigenetics. 2006, Cold Spring Harbor Laboratory Press.
5. Amabile, A., Migliara, A., Capasso, P., Biffi, M., Cittaro, D., Naldini, L., Lombardo, A., Inheritable silencing of endogenous genes by hit-and-run targeted epigenetic editing. Cell 167 (2016), 219–232.
6. Anton, T., Bultmann, S., Leonhardt, H., Markaki, Y., Visualization of specific DNA sequences in living mouse embryonic stem cells with a programmable fluorescent CRISPR/Cas system. Nucleus 5 (2014), 163–172.
7. Anton, T., Leonhardt, H., Markaki, Y., Visualization of genomic loci in living cells with a fluorescent CRISPR/Cas9 system. Methods Mol. Biol. 1411 (2016), 407–417.
8. A. Atala, R. Lanza, J. Thomson, and R. Nerem, eds. (2010). Principles of regenerative medicine (Elsevier/Academic Press), https://www.elsevier.com/books/principles-of-regenerative-medicine/atala/978-0-12-381422-7.
9. Audergon, P.N., Catania, S., Kagansky, A., Tong, P., Shukla, M., Pidoux, A.L., Allshire, R.C., Epigenetics. Restricted epigenetic inheritance of H3K9 methylation. Science 348 (2015), 132–135.
10. Balboa, D., Weltner, J., Eurola, S., Trokovic, R., Wartiovaara, K., Otonkoski, T., Conditionally stabilized dCas9 activator for controlling gene expression in human cell reprogramming and differentiation. Stem Cell Reports 5 (2015), 448–459.
11. Bernstein, B.E., Mikkelsen, T.S., Xie, X., Kamal, M., Huebert, D.J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125 (2006), 315–326.
12. Bestor, T.H., The DNA methyltransferases of mammals. Hum. Mol. Genet. 9 (2000), 2395–2402.
13. Bialek, J.K., Dunay, G.A., Voges, M., Schäfer, C., Spohn, M., Stucka, R., Hauber, J., Lange, U.C., Targeted HIV-1 latency reversal using CRISPR/Cas9-derived transcriptional activator systems. PLoS ONE, 11, 2016, e0158294.
14. Black, J.B., Adler, A.F., Wang, H.G., D'Ippolito, A.M., Hutchinson, H.A., Reddy, T.E., Pitt, G.S., Leong, K.W., Gersbach, C.A., Targeted epigenetic remodeling of endogenous loci by CRISPR/Cas9-based transcriptional activators directly converts fibroblasts to neuronal cells. Cell Stem Cell 19 (2016), 406–414.
15. Braun, C.J., Bruno, P.M., Horlbeck, M.A., Gilbert, L.A., Weissman, J.S., Hemann, M.T., Versatile in vivo regulation of tumor phenotypes by dCas9-mediated transcriptional perturbation. Proc. Natl. Acad. Sci. USA 113 (2016), E3892–E3900.
16. Bulger, M., Groudine, M., Enhancers: The abundance and function of regulatory sequences beyond promoters. Dev. Biol. 339 (2010), 250–257.
17. Byrum, S.D., Raman, A., Taverna, S.D., Tackett, A.J., ChAP-MS: A method for identification of proteins and histone posttranslational modifications at a single genomic locus. Cell Rep. 2 (2012), 198–205.
18. Caiazzo, M., Giannelli, S., Valente, P., Lignani, G., Carissimo, A., Sessa, A., Colasante, G., Bartolomeo, R., Massimino, L., Ferroni, S., et al. Direct conversion of fibroblasts into functional astrocytes by defined transcription factors. Stem Cell Reports 4 (2015), 25–36.
19. Cano-Rodriguez, D., Gjaltema, R.A., Jilderda, L.J., Jellema, P., Dokter-Fokkens, J., Ruiters, M.H., Rots, M.G., Writing of H3K4Me3 overcomes epigenetic silencing in a sustained but context-dependent manner. Nat. Commun., 7, 2016, 12284.
20. Canver, M.C., Smith, E.C., Sher, F., Pinello, L., Sanjana, N.E., Shalem, O., Chen, D.D., Schupp, P.G., Vinjamur, D.S., Garcia, S.P., et al. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature 527 (2015), 192–197.
21. Canver, M.C., Lessard, S., Pinello, L., Wu, Y., Ilboudo, Y., Stern, E.N., Needleman, A.J., Galactéros, F., Brugnara, C., Kutlar, A., et al. Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci. Nat Genet. 49 (2017), 625–634.
22. Capellera-Garcia, S., Pulecio, J., Dhulipala, K., Siva, K., Rayon-Estrada, V., Singbrant, S., Sommarin, M.N., Walkley, C.R., Soneji, S., Karlsson, G., et al. Defining the minimal factors required for erythropoiesis through direct lineage conversion. Cell Rep. 15 (2016), 2550–2562.
23. Cassidy, S.B., Schwartz, S., Prader-Willi and Angelman syndromes. Disorders of genomic imprinting. Medicine (Baltimore) 77 (1998), 140–151.
24. Cavalli, G., Paro, R., The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis. Cell 93 (1998), 505–518.
25. Chakraborty, S., Ji, H., Kabadi, A.M., Gersbach, C.A., Christoforou, N., Leong, K.W., A CRISPR/Cas9-based system for reprogramming cell lineage specification. Stem Cell Reports 3 (2014), 940–947.
26. Chavez, A., Tuttle, M., Pruitt, B.W., Ewen-Campen, B., Chari, R., Ter-Ovanesyan, D., Haque, S.J., Cecchi, R.J., Kowal, E.J.K., Buchthal, J., et al. Comparison of Cas9 activators in multiple species. Nat. Methods 13 (2016), 563–567.
27. Chedin, F., Lieber, M.R., Hsieh, C.L., The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc. Natl. Acad. Sci. USA 99 (2002), 16916–16921.
28. Chen, T., Dent, S.Y., Chromatin modifiers and remodellers: Regulators of cellular differentiation. Nat. Rev. Genet. 15 (2014), 93–106.
29. Chen, X., Xu, H., Yuan, P., Fang, F., Huss, M., Vega, V.B., Wong, E., Orlov, Y.L., Zhang, W., Jiang, J., et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133 (2008), 1106–1117.
30. Chen, B., Gilbert, L.A., Cimini, B.A., Schnitzbauer, J., Zhang, W., Li, G.W., Park, J., Blackburn, E.H., Weissman, J.S., Qi, L.S., Huang, B., Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155 (2013), 1479–1491.
31. Chen, B., Hu, J., Almeida, R., Liu, H., Balakrishnan, S., Covill-Cooke, C., Lim, W.A., Huang, B., Expanding the CRISPR imaging toolset with Staphylococcus aureus Cas9 for simultaneous imaging of multiple genomic loci. Nucleic Acids Res., 44, 2016, e75.
32. Cheng, A.W., Wang, H., Yang, H., Shi, L., Katz, Y., Theunissen, T.W., Rangarajan, S., Shivalila, C.S., Dadon, D.B., Jaenisch, R., Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Res. 23 (2013), 1163–1171.
33. Cheng, A.W., Jillette, N., Lee, P., Plaskon, D., Fujiwara, Y., Wang, W., Taghbalout, A., Wang, H., Casilio: A versatile CRISPR-Cas9-Pumilio hybrid for gene regulation and genomic labeling. Cell Res. 26 (2016), 254–257.
34. Choudhury, S.R., Cui, Y., Lubecka, K., Stefanska, B., Irudayaraj, J., CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. Oncotarget 7 (2016), 46545–46556.
35. Chylinski, K., Makarova, K.S., Charpentier, E., Koonin, E.V., Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res. 42 (2014), 6091–6105.
36. Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P.D., Wu, X., Jiang, W., Marraffini, L.A., Zhang, F., Multiplex genome engineering using CRISPR/Cas systems. Science 339 (2013), 819–823.
37. Cremer, M., von Hase, J., Volm, T., Brero, A., Kreth, G., Walter, J., Fischer, C., Solovei, I., Cremer, C., Cremer, T., Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells. Chromosome Res. 9 (2001), 541–567.
38. Croft, J.A., Bridger, J.M., Boyle, S., Perry, P., Teague, P., Bickmore, W.A., Differences in the localization and morphology of chromosomes in the human nucleus. J. Cell Biol. 145 (1999), 1119–1131.
39. Datlinger, P., Rendeiro, A.F., Schmidl, C., Krausgruber, T., Traxler, P., Klughammer, J., Schuster, L.C., Kuchler, A., Alpar, D., Bock, C., Pooled CRISPR screening with single-cell transcriptome readout. Nat. Methods 14 (2017), 297–301.
40. de Wit, E., de Laat, W., A decade of 3C technologies: Insights into nuclear organization. Genes Dev. 26 (2012), 11–24.
41. Dekker, J., Marti-Renom, M.A., Mirny, L.A., Exploring the three-dimensional organization of genomes: Interpreting chromatin interaction data. Nat. Rev. Genet. 14 (2013), 390–403.
42. Diao, Y., Li, B., Meng, Z., Jung, I., Lee, A.Y., Dixon, J., Maliskova, L., Guan, K.L., Shen, Y., Ren, B., A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening. Genome Res. 26 (2016), 397–405.
43. Dixit, A., Parnas, O., Li, B., Chen, J., Fulco, C.P., Jerby-Arnon, L., Marjanovic, N.D., Dionne, D., Burks, T., Raychowdhury, R., et al. Perturb-Seq: Dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. Cell 167 (2016), 1853–1866.
44. Du, D., Roguev, A., Gordon, D.E., Chen, M., Chen, S.H., Shales, M., Shen, J.P., Ideker, T., Mali, P., Qi, L.S., Krogan, N.J., Genetic interaction mapping in mammalian cells using CRISPR interference. Nat. Methods 14 (2017), 577–580.
45. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489 (2012), 57–74.
46. Ernst, J., Kellis, M., ChromHMM: Automating chromatin-state discovery and characterization. Nat. Methods 9 (2012), 215–216.
47. Essers, J., van Cappellen, W.A., Theil, A.F., van Drunen, E., Jaspers, N.G., Hoeijmakers, J.H., Wyman, C., Vermeulen, W., Kanaar, R., Dynamics of relative chromosome position during the cell cycle. Mol. Biol. Cell 16 (2005), 769–775.
48. Esvelt, K.M., Mali, P., Braff, J.L., Moosburner, M., Yaung, S.J., Church, G.M., Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. Nat. Methods 10 (2013), 1116–1121.
49. Farzadfard, F., Perli, S.D., Lu, T.K., Tunable and multifunctional eukaryotic transcription factors based on CRISPR/Cas. ACS Synth. Biol. 2 (2013), 604–613.
50. Fidalgo, M., Huang, X., Guallar, D., Sanchez-Priego, C., Valdes, V.J., Saunders, A., Ding, J., Wu, W.S., Clavel, C., Wang, J., Zfp281 coordinates opposing functions of Tet1 and Tet2 in pluripotent states. Cell Stem Cell 19 (2016), 355–369.
51. Flusberg, B.A., Webster, D.R., Lee, J.H., Travers, K.J., Olivares, E.C., Clark, T.A., Korlach, J., Turner, S.W., Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat. Methods 7 (2010), 461–465.
52. Fonfara, I., Le Rhun, A., Chylinski, K., Makarova, K.S., Lécrivain, A.L., Bzdrenga, J., Koonin, E.V., Charpentier, E., Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems. Nucleic Acids Res. 42 (2014), 2577–2590.
53. Fujita, T., Fujii, H., Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR. Biochem. Biophys. Res. Commun. 439 (2013), 132–136.
54. Fujita, T., Fujii, H., Isolation of specific genomic regions and identification of associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR. Methods Mol. Biol. 1288 (2015), 43–52.
55. Fulco, C.P., Munschauer, M., Anyoha, R., Munson, G., Grossman, S.R., Perez, E.M., Kane, M., Cleary, B., Lander, E.S., Engreitz, J.M., Systematic mapping of functional enhancer-promoter connections with CRISPR interference. Science 354 (2016), 769–773.
56. Gao, R., Dong, R., Du, J., Ma, P., Wang, S., Fan, Z., Depletion of histone demethylase KDM2A inhibited cell proliferation of stem cells from apical papilla by de-repression of p15INK4B and p27Kip1. Mol. Cell. Biochem. 379 (2013), 115–122.
57. Gao, Y., Xiong, X., Wong, S., Charles, E.J., Lim, W.A., Qi, L.S., Complex transcriptional modulation with orthogonal and inducible dCas9 regulators. Nat. Methods 13 (2016), 1043–1049.
58. Garcia-Bloj, B., Moses, C., Sgro, A., Plani-Lam, J., Arooj, M., Duffy, C., Thiruvengadam, S., Sorolla, A., Rashwan, R., Mancera, R.L., et al. Waking up dormant tumor suppressor genes with zinc fingers, TALEs and the CRISPR/dCas9 system. Oncotarget 7 (2016), 60535–60554.
59. Gardiner-Garden, M., Frommer, M., CpG islands in vertebrate genomes. J. Mol. Biol. 196 (1987), 261–282.
60. Genga, R.M., Kearns, N.A., Maehr, R., Controlling transcription in human pluripotent stem cells using CRISPR-effectors. Methods 101 (2016), 36–42.
61. Gifford, C.A., Ziller, M.J., Gu, H., Trapnell, C., Donaghey, J., Tsankov, A., Shalek, A.K., Kelley, D.R., Shishkin, A.A., Issner, R., et al. Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell 153 (2013), 1149–1163.
62. Gilbert, L.A., Larson, M.H., Morsut, L., Liu, Z., Brar, G.A., Torres, S.E., Stern-Ginossar, N., Brandman, O., Whitehead, E.H., Doudna, J.A., et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154 (2013), 442–451.
63. Gilbert, L.A., Horlbeck, M.A., Adamson, B., Villalta, J.E., Chen, Y., Whitehead, E.H., Guimaraes, C., Panning, B., Ploegh, H.L., Bassik, M.C., et al. Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation. Cell 159 (2014), 647–661.
64. González, F., Zhu, Z., Shi, Z.D., Lelli, K., Verma, N., Li, Q.V., Huangfu, D., An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells. Cell Stem Cell 15 (2014), 215–226.
65. Goodman, R.H., Smolik, S., CBP/p300 in cell growth, transformation, and development. Genes Dev. 14 (2000), 1553–1577.
66. Graf, T., Enver, T., Forcing cells to change lineages. Nature 462 (2009), 587–594.
67. Grewal, S.I., Klar, A.J., Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell 86 (1996), 95–101.
68. Groner, A.C., Meylan, S., Ciuffi, A., Zangger, N., Ambrosini, G., Dénervaud, N., Bucher, P., Trono, D., KRAB-zinc finger proteins and KAP1 can mediate long-range transcriptional repression through heterochromatin spreading. PLoS Genet., 6, 2010, e1000869.
69. Guilinger, J.P., Thompson, D.B., Liu, D.R., Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 32 (2014), 577–582.
70. Hellwig, D., Münch, S., Orthaus, S., Hoischen, C., Hemmerich, P., Diekmann, S., Live-cell imaging reveals sustained centromere binding of CENP-T via CENP-A and CENP-B. J. Biophotonics 1 (2008), 245–254.
71. Hilton, I.B., D'Ippolito, A.M., Vockley, C.M., Thakore, P.I., Crawford, G.E., Reddy, T.E., Gersbach, C.A., Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat. Biotechnol. 33 (2015), 510–517.
72. Himeda, C.L., Jones, T.I., Jones, P.L., CRISPR/dCas9-mediated transcriptional inhibition ameliorates the epigenetic dysregulation at D4Z4 and represses DUX4-fl in FSH muscular dystrophy. Mol. Ther. 24 (2016), 527–535.
73. Ho, S.M., Hartley, B.J., Flaherty, E., Rajarajan, P., Abdelaal, R., Obiorah, I., Barretto, N., Muhammad, H., Phatnani, H.P., Akbarian, S., Brennand, K.J., Evaluating synthetic activation and repression of neuropsychiatric-related genes in hiPSC-derived NPCs, neurons, and astrocytes. Stem Cell Reports 9 (2017), 615–628.
74. Holoch, D., Moazed, D., RNA-mediated epigenetic regulation of gene expression. Nat. Rev. Genet. 16 (2015), 71–84.
75. Horlbeck, M.A., Gilbert, L.A., Villalta, J.E., Adamson, B., Pak, R.A., Chen, Y., Fields, A.P., Park, C.Y., Corn, J.E., Kampmann, M., Weissman, J.S., Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. eLife, 2016, 10.7554/eLife.19760 Published online September 23, 2016.
76. Horlbeck, M.A., Witkowsky, L.B., Guglielmi, B., Replogle, J.M., Gilbert, L.A., Villalta, J.E., Torigoe, S.E., Tjian, R., Weissman, J.S., Nucleosomes impede Cas9 access to DNA in vivo and in vitro. eLife, 5, 2016, 5.
77. Hou, Z., Zhang, Y., Propson, N.E., Howden, S.E., Chu, L.F., Sontheimer, E.J., Thomson, J.A., Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc. Natl. Acad. Sci. USA 110 (2013), 15644–15649.
78. Hsu, P.D., Lander, E.S., Zhang, F., Development and applications of CRISPR-Cas9 for genome engineering. Cell 157 (2014), 1262–1278.
79. Hu, J., Lei, Y., Wong, W.K., Liu, S., Lee, K.C., He, X., You, W., Zhou, R., Guo, J.T., Chen, X., et al. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors. Nucleic Acids Res. 42 (2014), 4375–4390.
80. Hu, H., Luo, C., Zheng, Y.G., Transient kinetics define a complete kinetic model for protein arginine methyltransferase 1. J. Biol. Chem. 291 (2016), 26722–26738.
81. Huang, H., Maertens, A.M., Hyland, E.M., Dai, J., Norris, A., Boeke, J.D., Bader, J.S., HistoneHits: A database for histone mutations and their phenotypes. Genome Res. 19 (2009), 674–681.
82. Huypens, P., Sass, S., Wu, M., Dyckhoff, D., Tschöp, M., Theis, F., Marschall, S., Hrabě de Angelis, M., Beckers, J., Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nat. Genet. 48 (2016), 497–499.
83. Jaitin, D.A., Weiner, A., Yofe, I., Lara-Astiaso, D., Keren-Shaul, H., David, E., Salame, T.M., Tanay, A., van Oudenaarden, A., Amit, I., Dissecting immune circuits by linking CRISPR-pooled screens with single-cell RNA-seq. Cell 167 (2016), 1883–1896.
84. Jenuwein, T., Allis, C.D., Translating the histone code. Science 293 (2001), 1074–1080.
85. Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A., Charpentier, E., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337 (2012), 816–821.
86. Kearns, N.A., Genga, R.M., Enuameh, M.S., Garber, M., Wolfe, S.A., Maehr, R., Cas9 effector-mediated regulation of transcription and differentiation in human pluripotent stem cells. Development 141 (2014), 219–223.
87. Kearns, N.A., Pham, H., Tabak, B., Genga, R.M., Silverstein, N.J., Garber, M., Maehr, R., Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat. Methods 12 (2015), 401–403.
88. Kelly, T.K., De Carvalho, D.D., Jones, P.A., Epigenetic modifications as therapeutic targets. Nat. Biotechnol. 28 (2010), 1069–1078.
89. Keung, A.J., Joung, J.K., Khalil, A.S., Collins, J.J., Chromatin regulation at the frontier of synthetic biology. Nat. Rev. Genet. 16 (2015), 159–171.
90. Kim, K., Doi, A., Wen, B., Ng, K., Zhao, R., Cahan, P., Kim, J., Aryee, M.J., Ji, H., Ehrlich, Ll, et al. Epigenetic memory in induced pluripotent stem cells. Nature 467 (2010), 285–290.
91. Kim, J.M., Kim, K., Schmidt, T., Punj, V., Tucker, H., Rice, J.C., Ulmer, T.S., An, W., Cooperation between SMYD3 and PC4 drives a distinct transcriptional program in cancer cells. Nucleic Acids Res. 43 (2015), 8868–8883.
92. Kind, J., Pagie, L., Ortabozkoyun, H., Boyle, S., de Vries, S.S., Janssen, H., Amendola, M., Nolen, L.D., Bickmore, W.A., van Steensel, B., Single-cell dynamics of genome-nuclear lamina interactions. Cell 153 (2013), 178–192.
93. Klann, T.S., Black, J.B., Chellappan, M., Safi, A., Song, L., Hilton, I.B., Crawford, G.E., Reddy, T.E., Gersbach, C.A., CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome. Nat. Biotechnol. 35 (2017), 561–568.
94. Kleinstiver, B.P., Prew, M.S., Tsai, S.Q., Topkar, V.V., Nguyen, N.T., Zheng, Z., Gonzales, A.P., Li, Z., Peterson, R.T., Yeh, J.R., et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523 (2015), 481–485.
95. Klosin, A., Casas, E., Hidalgo-Carcedo, C., Vavouri, T., Lehner, B., Transgenerational transmission of environmental information in C. elegans. Science 356 (2017), 320–323.
96. Knight, S.C., Xie, L., Deng, W., Guglielmi, B., Witkowsky, L.B., Bosanac, L., Zhang, E.T., El Beheiry, M., Masson, J.B., Dahan, M., et al. Dynamics of CRISPR-Cas9 genome interrogation in living cells. Science 350 (2015), 823–826.
97. Koerner, M.V., Pauler, F.M., Huang, R., Barlow, D.P., The function of non-coding RNAs in genomic imprinting. Development 136 (2009), 1771–1783.
98. Koike-Yusa, H., Li, Y., Tan, E.P., Velasco-Herrera, Mdel.C., Yusa, K., Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat. Biotechnol. 32 (2014), 267–273.
99. Komor, A.C., Badran, A.H., Liu, D.R., CRISPR-based technologies for the manipulation of eukaryotic genomes. Cell 168 (2017), 20–36.
100. Konermann, S., Brigham, M.D., Trevino, A.E., Joung, J., Abudayyeh, O.O., Barcena, C., Hsu, P.D., Habib, N., Gootenberg, J.S., Nishimasu, H., et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517 (2015), 583–588.
101. Korkmaz, G., Lopes, R., Ugalde, A.P., Nevedomskaya, E., Han, R., Myacheva, K., Zwart, W., Elkon, R., Agami, R., Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Nat. Biotechnol. 34 (2016), 192–198.
102. Kouzarides, T., Chromatin modifications and their function. Cell 128 (2007), 693–705.
103. Kwon, D.Y., Zhao, Y.T., Lamonica, J.M., Zhou, Z., Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC. Nat. Commun., 8, 2017, 15315.
104. Lane, A.B., Strzelecka, M., Ettinger, A., Grenfell, A.W., Wittmann, T., Heald, R., Enzymatically generated CRISPR libraries for genome labeling and screening. Dev. Cell 34 (2015), 373–378.
105. Lei, Y., Zhang, X., Su, J., Jeong, M., Gundry, M.C., Huang, Y.H., Zhou, Y., Li, W., Goodell, M.A., Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein. Nat. Commun., 8, 2017, 16026.
106. Li, G., Ruan, X., Auerbach, R.K., Sandhu, K.S., Zheng, M., Wang, P., Poh, H.M., Goh, Y., Lim, J., Zhang, J., et al. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148 (2012), 84–98.
107. Li, Y., Rivera, C.M., Ishii, H., Jin, F., Selvaraj, S., Lee, A.Y., Dixon, J.R., Ren, B., CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. PLoS ONE, 9, 2014, e114485.
108. Lindhout, B.I., Fransz, P., Tessadori, F., Meckel, T., Hooykaas, P.J., van der Zaal, B.J., Live cell imaging of repetitive DNA sequences via GFP-tagged polydactyl zinc finger proteins. Nucleic Acids Res., 35, 2007, e107.
109. Liu, X.S., Wu, H., Ji, X., Stelzer, Y., Wu, X., Czauderna, S., Shu, J., Dadon, D., Young, R.A., Jaenisch, R., Editing DNA methylation in the mammalian genome. Cell 167 (2016), 233–247.
110. Long, C., Amoasii, L., Mireault, A.A., McAnally, J.R., Li, H., Sanchez-Ortiz, E., Bhattacharyya, S., Shelton, J.M., Bassel-Duby, R., Olson, E.N., Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 351 (2016), 400–403.
111. López Rodríguez, M., Kaminska, D., Lappalainen, K., Pihlajamäki, J., Kaikkonen, M.U., Laakso, M., Identification and characterization of a FOXA2-regulated transcriptional enhancer at a type 2 diabetes intronic locus that controls GCKR expression in liver cells. Genome Med., 9, 2017, 63.
112. Ma, H., Reyes-Gutierrez, P., Pederson, T., Visualization of repetitive DNA sequences in human chromosomes with transcription activator-like effectors. Proc. Natl. Acad. Sci. USA 110 (2013), 21048–21053.
113. Ma, H., Naseri, A., Reyes-Gutierrez, P., Wolfe, S.A., Zhang, S., Pederson, T., Multicolor CRISPR labeling of chromosomal loci in human cells. Proc. Natl. Acad. Sci. USA 112 (2015), 3002–3007.
114. Ma, H., Tu, L.C., Naseri, A., Huisman, M., Zhang, S., Grunwald, D., Pederson, T., Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow. Nat. Biotechnol. 34 (2016), 528–530.
115. Maeder, M.L., Linder, S.J., Cascio, V.M., Fu, Y., Ho, Q.H., Joung, J.K., CRISPR RNA-guided activation of endogenous human genes. Nat. Methods 10 (2013), 977–979.
116. Mali, P., Aach, J., Stranges, P.B., Esvelt, K.M., Moosburner, M., Kosuri, S., Yang, L., Church, G.M., CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol. 31 (2013), 833–838.
117. Mali, P., Esvelt, K.M., Church, G.M., Cas9 as a versatile tool for engineering biology. Nat. Methods 10 (2013), 957–963.
118. Mandal, P.K., Rossi, D.J., Reprogramming human fibroblasts to pluripotency using modified mRNA. Nat. Protoc. 8 (2013), 568–582.
119. Mandegar, M.A., Huebsch, N., Frolov, E.B., Shin, E., Truong, A., Olvera, M.P., Chan, A.H., Miyaoka, Y., Holmes, K., Spencer, C.I., et al. CRISPR interference efficiently induces specific and reversible gene silencing in human iPSCs. Cell Stem Cell 18 (2016), 541–553.
120. Maurano, M.T., Humbert, R., Rynes, E., Thurman, R.E., Haugen, E., Wang, H., Reynolds, A.P., Sandstrom, R., Qu, H., Brody, J., et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337 (2012), 1190–1195.
121. McDonald, J.I., Celik, H., Rois, L.E., Fishberger, G., Fowler, T., Rees, R., Kramer, A., Martens, A., Edwards, J.R., Challen, G.A., Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation. Biol. Open 5 (2016), 866–874.
122. Melo, C.A., Drost, J., Wijchers, P.J., van de Werken, H., de Wit, E., Oude Vrielink, J.A., Elkon, R., Melo, S.A., Léveillé, N., Kalluri, R., et al. eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol. Cell 49 (2013), 524–535.
123. Mikkelsen, T.S., Ku, M., Jaffe, D.B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.K., Koche, R.P., et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448 (2007), 553–560.
124. Milite, C., Feoli, A., Sasaki, K., La Pietra, V., Balzano, A.L., Marinelli, L., Mai, A., Novellino, E., Castellano, S., Tosco, A., Sbardella, G., A novel cell-permeable, selective, and noncompetitive inhibitor of KAT3 histone acetyltransferases from a combined molecular pruning/classical isosterism approach. J. Med. Chem. 58 (2015), 2779–2798.
125. Misteli, T., Beyond the sequence: Cellular organization of genome function. Cell 128 (2007), 787–800.
126. Misteli, T., The cell biology of genomes: Bringing the double helix to life. Cell 152 (2013), 1209–1212.
127. Miyanari, Y., Ziegler-Birling, C., Torres-Padilla, M.E., Live visualization of chromatin dynamics with fluorescent TALEs. Nat. Struct. Mol. Biol. 20 (2013), 1321–1324.
128. Morita, S., Noguchi, H., Horii, T., Nakabayashi, K., Kimura, M., Okamura, K., Sakai, A., Nakashima, H., Hata, K., Nakashima, K., Hatada, I., Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions. Nat. Biotechnol. 34 (2016), 1060–1065.
129. Nashun, B., Hill, P.W., Hajkova, P., Reprogramming of cell fate: epigenetic memory and the erasure of memories past. EMBO J 34 (2015), 1296–1308.
130. Nelson, C.E., Hakim, C.H., Ousterout, D.G., Thakore, P.I., Moreb, E.A., Castellanos Rivera, R.M., Madhavan, S., Pan, X., Ran, F.A., Yan, W.X., et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351 (2016), 403–407.
131. Nihongaki, Y., Yamamoto, S., Kawano, F., Suzuki, H., Sato, M., CRISPR-Cas9-based photoactivatable transcription system. Chem. Biol. 22 (2015), 169–174.
132. Nishizawa, M., Chonabayashi, K., Nomura, M., Tanaka, A., Nakamura, M., Inagaki, A., Nishikawa, M., Takei, I., Oishi, A., Tanabe, K., Ohnuki, M., et al. Epigenetic variation between human induced pluripotent stem cell lines is an indicator of differentiation capacity. Cell Stem Cell 19 (2016), 341–354.
133. Nissim, L., Perli, S.D., Fridkin, A., Perez-Pinera, P., Lu, T.K., Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells. Mol. Cell 54 (2014), 698–710.
134. Oldridge, D.A., Wood, A.C., Weichert-Leahey, N., Crimmins, I., Sussman, R., Winter, C., McDaniel, L.D., Diamond, M., Hart, L.S., Zhu, S., et al. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature 528 (2015), 418–421.
135. Panning, B., Dausman, J., Jaenisch, R., X chromosome inactivation is mediated by Xist RNA stabilization. Cell 90 (1997), 907–916.
136. Pastor, W.A., Aravind, L., Rao, A., TETonic shift: Biological roles of TET proteins in DNA demethylation and transcription. Nat. Rev. Mol. Cell Biol. 14 (2013), 341–356.
137. Pengue, G., Lania, L., Krüppel-associated box-mediated repression of RNA polymerase II promoters is influenced by the arrangement of basal promoter elements. Proc. Natl. Acad. Sci. USA 93 (1996), 1015–1020.
138. Pennisi, E., Long noncoding RNAs may alter chromosome's 3D structure. Science, 340, 2013, 910.
139. Perez-Pinera, P., Ousterout, D.G., Gersbach, C.A., Advances in targeted genome editing. Curr. Opin. Chem. Biol. 16 (2012), 268–277.
140. Perez-Pinera, P., Kocak, D.D., Vockley, C.M., Adler, A.F., Kabadi, A.M., Polstein, L.R., Thakore, P.I., Glass, K.A., Ousterout, D.G., Leong, K.W., et al. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat. Methods 10 (2013), 973–976.
141. Polstein, L.R., Gersbach, C.A., A light-inducible CRISPR-Cas9 system for control of endogenous gene activation. Nat. Chem. Biol. 11 (2015), 198–200.
142. Polstein, L.R., Perez-Pinera, P., Kocak, D.D., Vockley, C.M., Bledsoe, P., Song, L., Safi, A., Crawford, G.E., Reddy, T.E., Gersbach, C.A., Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators. Genome Res. 25 (2015), 1158–1169.
143. Pradeepa, M.M., Grimes, G.R., Kumar, Y., Olley, G., Taylor, G.C., Schneider, R., Bickmore, W.A., Histone H3 globular domain acetylation identifies a new class of enhancers. Nat. Genet. 48 (2016), 681–686.
144. Pulecio, J., Nivet, E., Sancho-Martinez, I., Vitaloni, M., Guenechea, G., Xia, Y., Kurian, L., Dubova, I., Bueren, J., Laricchia-Robbio, L., Belmonte, J.C.I., Conversion of human fibroblasts into monocyte-like progenitor cells. Stem Cells 32 (2014), 2923–2938.
145. Pulecio, J., Alejo-Valle, O., Capellera-Garcia, S., Vitaloni, M., Rio, P., Mejía-Ramírez, E., Caserta, I., Bueren, J.A., Flygare, J., Raya, A., Direct conversion of fibroblasts to megakaryocyte progenitors. Cell Rep. 17 (2016), 671–683.
146. Qi, L.S., Larson, M.H., Gilbert, L.A., Doudna, J.A., Weissman, J.S., Arkin, A.P., Lim, W.A., Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152 (2013), 1173–1183.
147. Radzisheuskaya, A., Shlyueva, D., Müller, I., Helin, K., Optimizing sgRNA position markedly improves the efficiency of CRISPR/dCas9-mediated transcriptional repression. Nucleic Acids Res., 44, 2016, e141.
148. Ragunathan, K., Jih, G., Moazed, D., Epigenetics. Epigenetic inheritance uncoupled from sequence-specific recruitment. Science, 348, 2015, 1258699.
149. Rajagopal, N., Srinivasan, S., Kooshesh, K., Guo, Y., Edwards, M.D., Banerjee, B., Syed, T., Emons, B.J., Gifford, D.K., Sherwood, R.I., High-throughput mapping of regulatory DNA. Nat. Biotechnol. 34 (2016), 167–174.
150. Rakyan, V.K., Down, T.A., Balding, D.J., Beck, S., Epigenome-wide association studies for common human diseases. Nat. Rev. Genet. 12 (2011), 529–541.
151. Ramos-Mejía, V., Montes, R., Bueno, C., Ayllón, V., Real, P.J., Rodríguez, R., Menendez, P., Residual expression of the reprogramming factors prevents differentiation of iPSC generated from human fibroblasts and cord blood CD34+ progenitors. PLoS One, 7, 2012, e35824.
152. Rasmussen, K.D., Helin, K., Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 30 (2016), 733–750.
153. Riethoven, J.J., Regulatory regions in DNA: promoters, enhancers, silencers, and insulators. Method Mol. Biol. 674 (2010), 33–42.
154. Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. Integrative analysis of 111 reference human epigenomes. Nature 518 (2015), 317–330.
155. Robinett, C.C., Straight, A., Li, G., Willhelm, C., Sudlow, G., Murray, A., Belmont, A.S., In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition. J. Cell Biol. 135 (1996), 1685–1700.
156. Rodríguez-Campos, A., Azorín, F., RNA is an integral component of chromatin that contributes to its structural organization. PLoS ONE, 2, 2007, e1182.
157. Sakuma, T., Nishikawa, A., Kume, S., Chayama, K., Yamamoto, T., Multiplex genome engineering in human cells using all-in-one CRISPR/Cas9 vector system. Sci. Rep., 4, 2014, 5400.
158. Sanjana, N.E., Wright, J., Zheng, K., Shalem, O., Fontanillas, P., Joung, J., Cheng, C., Regev, A., Zhang, F., High-resolution interrogation of functional elements in the noncoding genome. Science 353 (2016), 1545–1549.
159. Sanyal, A., Lajoie, B.R., Jain, G., Dekker, J., The long-range interaction landscape of gene promoters. Nature 489 (2012), 109–113.
160. Scacheri, C.A., Scacheri, P.C., Mutations in the noncoding genome. Curr. Opin. Pediatr. 27 (2015), 659–664.
161. Shalem, O., Sanjana, N.E., Hartenian, E., Shi, X., Scott, D.A., Mikkelson, T., Heckl, D., Ebert, B.L., Root, D.E., Doench, J.G., Zhang, F., Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343 (2014), 84–87.
162. Shalem, O., Sanjana, N.E., Zhang, F., High-throughput functional genomics using CRISPR-Cas9. Nat. Rev. Genet. 16 (2015), 299–311.
163. Shao, S., Zhang, W., Hu, H., Xue, B., Qin, J., Sun, C., Sun, Y., Wei, W., Sun, Y., Long-term dual-color tracking of genomic loci by modified sgRNAs of the CRISPR/Cas9 system. Nucleic Acids Res., 44, 2016, e86.
164. Shechner, D.M., Hacisuleyman, E., Younger, S.T., Rinn, J.L., Multiplexable, locus-specific targeting of long RNAs with CRISPR-Display. Nat. Methods 12 (2015), 664–670.
165. Simeonov, D.R., Gowen, B.G., Boontanrart, M., Roth, T.L., Gagnon, J.D., Mumbach, M.R., Satpathy, A.T., Lee, Y., Bray, N.L., Chan, A.Y., et al. Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature 549 (2017), 111–115.
166. Smith, Z.D., Meissner, A., DNA methylation: Roles in mammalian development. Nat. Rev. Genet. 14 (2013), 204–220.
167. Stark, C., Breitkreutz, B.J., Chatr-Aryamontri, A., Boucher, L., Oughtred, R., Livstone, M.S., Nixon, J., Van Auken, K., Wang, X., Shi, X., et al. The BioGRID Interaction Database: 2011 update. Nucleic Acids Res. 39 (2011), D698–D704.
168. Stepper, P., Kungulovski, G., Jurkowska, R.Z., Chandra, T., Krueger, F., Reinhardt, R., Reik, W., Jeltsch, A., Jurkowski, T.P., Efficient targeted DNA methylation with chimeric dCas9-Dnmt3a-Dnmt3L methyltransferase. Nucleic Acids Res. 45 (2017), 1703–1713.
169. Swiech, L., Heidenreich, M., Banerjee, A., Habib, N., Li, Y., Trombetta, J., Sur, M., Zhang, F., In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nat. Biotechnol. 33 (2015), 102–106.
170. Tabebordbar, M., Zhu, K., Cheng, J.K.W., Chew, W.L., Widrick, J.J., Yan, W.X., Maesner, C., Wu, E.Y., Xiao, R., Ran, F.A., et al. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 351 (2016), 407–411.
171. Tanenbaum, M.E., Gilbert, L.A., Qi, L.S., Weissman, J.S., Vale, R.D., A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159 (2014), 635–646.
172. Thakore, P.I., D'Ippolito, A.M., Song, L., Safi, A., Shivakumar, N.K., Kabadi, A.M., Reddy, T.E., Crawford, G.E., Gersbach, C.A., Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements. Nat. Methods 12 (2015), 1143–1149.
173. Thakore, P.I., Black, J.B., Hilton, I.B., Gersbach, C.A., Editing the epigenome: Technologies for programmable transcription and epigenetic modulation. Nat. Methods 13 (2016), 127–137.
174. Thanisch, K., Schneider, K., Morbitzer, R., Solovei, I., Lahaye, T., Bultmann, S., Leonhardt, H., Targeting and tracing of specific DNA sequences with dTALEs in living cells. Nucleic Acids Res., 42, 2014, e38.
175. Tsai, S.Q., Wyvekens, N., Khayter, C., Foden, J.A., Thapar, V., Reyon, D., Goodwin, M.J., Aryee, M.J., Joung, J.K., Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat. Biotechnol. 32 (2014), 569–576.
176. Vitaloni, M., Pulecio, J., Bilic, J., Kuebler, B., Laricchia-Robbio, L., Izpisua Belmonte, J.C., MicroRNAs contribute to induced pluripotent stem cell somatic donor memory. J Biol Chem. 289 (2014), 2084–2098.
177. Vojta, A., Dobrinić, P., Tadić, V., Bočkor, L., Korać, P., Julg, B., Klasić, M., Zoldoš, V., Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Res. 44 (2016), 5615–5628.
178. Waldrip, Z.J., Byrum, S.D., Storey, A.J., Gao, J., Byrd, A.K., Mackintosh, S.G., Wahls, W.P., Taverna, S.D., Raney, K.D., Tackett, A.J., A CRISPR-based approach for proteomic analysis of a single genomic locus. Epigenetics 9 (2014), 1207–1211.
179. Wang, D., Garcia-Bassets, I., Benner, C., Li, W., Su, X., Zhou, Y., Qiu, J., Liu, W., Kaikkonen, M.U., Ohgi, K.A., et al. Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474 (2011), 390–394.
180. Wang, W., Li, G.W., Chen, C., Xie, X.S., Zhuang, X., Chromosome organization by a nucleoid-associated protein in live bacteria. Science 333 (2011), 1445–1449.
181. Wang, T., Wei, J.J., Sabatini, D.M., Lander, E.S., Genetic screens in human cells using the CRISPR-Cas9 system. Science 343 (2014), 80–84.
182. Weinberger, L., Ayyash, M., Novershtern, N., Hanna, J.H., Dynamic stem cell states: Naive to primed pluripotency in rodents and humans. Nat. Rev. Mol. Cell Biol. 17 (2016), 155–169.
183. Wu, H., Zhang, Y., Reversing DNA methylation: Mechanisms, genomics, and biological functions. Cell 156 (2014), 45–68.
184. Wu, T.P., Wang, T., Seetin, M.G., Lai, Y., Zhu, S., Lin, K., Liu, Y., Byrum, S.D., Mackintosh, S.G., Zhong, M., et al. DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature 532 (2016), 329–333.
185. Xie, W., Schultz, M.D., Lister, R., Hou, Z., Rajagopal, N., Ray, P., Whitaker, J.W., Tian, S., Hawkins, R.D., Leung, D., et al. Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153 (2013), 1134–1148.
186. Xiong, K., Zhou, Y., Hyttel, P., Bolund, L., Freude, K.K., Luo, Y., Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM). Stem Cell Res. (Amst.) 17 (2016), 665–669.
187. Xiong, T., Meister, G.E., Workman, R.E., Kato, N.C., Spellberg, M.J., Turker, F., Timp, W., Ostermeier, M., Novina, C.D., Targeted DNA methylation in human cells using engineered dCas9-methyltransferases. Sci. Rep., 7, 2017, 6732.
188. Xu, X., Tao, Y., Gao, X., Zhang, L., Li, X., Zou, W., Ruan, K., Wang, F., Xu, G.L., Hu, R., A CRISPR-based approach for targeted DNA demethylation. Cell Discov., 2, 2016, 16009.
189. Yang, Y., Wang, L., Bell, P., McMenamin, D., He, Z., White, J., Yu, H., Xu, C., Morizono, H., Musunuru, K., et al. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat. Biotechnol. 34 (2016), 334–338.
190. Yoshioka, S., Fujii, W., Ogawa, T., Sugiura, K., Naito, K., Development of a mono-promoter-driven CRISPR/Cas9 system in mammalian cells. Sci. Rep., 5, 2015, 18341.
191. Yuan, K., Shermoen, A.W., O'Farrell, P.H., Illuminating DNA replication during Drosophila development using TALE-lights. Curr. Biol. 24 (2014), R144–R145.
192. Zalatan, J.G., Lee, M.E., Almeida, R., Gilbert, L.A., Whitehead, E.H., La Russa, M., Tsai, J.C., Weissman, J.S., Dueber, J.E., Qi, L.S., Lim, W.A., Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell 160 (2015), 339–350.
193. Zhang, H., Gayen, S., Xiong, J., Zhou, B., Shanmugam, A.K., Sun, Y., Karatas, H., Liu, L., Rao, R.C., Wang, S., et al. MLL1 inhibition reprograms epiblast stem cells to naive pluripotency. Cell Stem Cell 18 (2016), 481–494.
194. Zhou, Y., Zhu, S., Cai, C., Yuan, P., Li, C., Huang, Y., Wei, W., High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature 509 (2014), 487–491.