Imaging Specific Genomic DNA in Living Cells

Annual Review of Biophysics

Volumn 45, Issue , 2016, Pages 1-23

  Chen, Baohui ^a   Guan, Juan ^a   Huang, Bo ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cas9; chromatin; CRISPR; fluorescence; microscopy; nucleus

Indexed keywords

CELLULAR APOPTOSIS SUSCEPTIBILITY PROTEIN; CRISPR ASSOCIATED PROTEIN; CRISPR ASSOCIATED PROTEIN 9; GENOMIC DNA; PROTEIN; RNA; TRANSCRIPTION ACTIVATOR LIKE EFFECTOR; TRANSCRIPTION ACTIVATOR LIKE EFFECTOR NUCLEASE; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN; DNA;

ANEUPLOIDY; ARTICLE; CELL LABELING; CELLS; CHROMATIN; CHROMOSOME STRUCTURE; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; COMPLEX FORMATION; DNA DAMAGE; DNA REPAIR; DNA SEQUENCE; FLUORESCENCE IMAGING; GENE DOSAGE; GENE EXPRESSION; GENE REARRANGEMENT; GENETIC RECOMBINATION; GENOME; GENOMIC INSTABILITY; HUMAN; IMAGING; MOLECULAR BIOLOGY; NONHUMAN; PRIORITY JOURNAL; ANIMAL; CRISPR CAS SYSTEM; GENETICS; METABOLISM; MOLECULAR IMAGING; PROCEDURES;

ANIMALS; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS; CRISPR-ASSOCIATED PROTEINS; CRISPR-CAS SYSTEMS; DNA; GENE DOSAGE; GENOME; HUMANS; MOLECULAR IMAGING;

EID: 84978434575     PISSN: 1936122X     EISSN: 19361238     Source Type: Book Series    
DOI: 10.1146/annurev-biophys-062215-010830     Document Type: Article

References (164)

1. Anton T, Bultmann S, Leonhardt H, Markaki Y. 2014. Visualization of specific DNA sequences in living mouse embryonic stem cells with a programmable fluorescent CRISPR/Cas system. Nucleus 5:163-72
2. Avner P, Heard E. 2001. X-chromosome inactivation: counting, choice and initiation. Nat. Rev. Genet. 2:59-67
3. Bancaud A, Huet S, Daigle N, Mozziconacci J, Beaudouin J, Ellenberg J. 2009. Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin. EMBO J. 28:3785-98
4. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, et al. 2007. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315:1709-12
5. Beerli RR, Barbas CF 3rd. 2002. Engineering polydactyl zinc-finger transcription factors. Nat. Biotechnol. 20:135-41
6. Beliveau BJ, Boettiger AN, Avendano MS, Jungmann R, McCole RB, et al. 2015. Single-molecule superresolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes. Nat. Commun. 6:7147
7. Belmont AS. 2001. Visualizing chromosome dynamics with GFP. Trends Cell Biol. 11:250-57
8. Belmont AS, Braunfeld MB, Sedat JW, Agard DA. 1989. Large-scale chromatin structural domains within mitotic and interphase chromosomes in vivo and in vitro. Chromosoma 98:129-43
9. Berger AB, Cabal GG, Fabre E, Duong T, Buc H, et al. 2008. High-resolution statistical mapping reveals gene territories in live yeast. Nat. Methods 5:1031-37
10. Beumer K, Bhattacharyya G, Bibikova M, Trautman JK, Carroll D. 2006. Efficient gene targeting in Drosophila with zinc-finger nucleases. Genetics 172:2391-403
11. Bibikova M, Beumer K, Trautman JK, Carroll D. 2003. Enhancing gene targeting with designed zinc finger nucleases. Science 300:764
12. Bickmore WA, van Steensel B. 2013. Genome architecture: domain organization of interphase chromosomes. Cell 152:1270-84
13. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, et al. 2009. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326:1509-12
14. Boettiger AN, Bintu B, Moffitt JR, Wang S, Beliveau BJ, et al. 2016. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529:418-22
15. Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, et al. 2005. Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLOS Biol. 3:826-42
16. Branzei D, Foiani M. 2008. Regulation of DNA repair throughout the cell cycle. Nat. Rev. Mol. Cell Biol. 9:297-308
17. Briggs AW, Rios X, Chari R, Yang L, Zhang F, et al. 2012. Iterative capped assembly: rapid and scalable synthesis of repeat-module DNA such as TAL effectors from individual monomers. Nucleic Acids Res. 40:e117
18. Brouns SJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJ, et al. 2008. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321:960-64
19. Bultmann S, Morbitzer R, Schmidt CS, Thanisch K, Spada F, et al. 2012. Targeted transcriptional activation of silent oct4 pluripotency gene by combining designer TALEs and inhibition of epigenetic modifiers. Nucleic Acids Res. 40:5368-77
20. Casas-Delucchi CS, Becker A, Bolius JJ, Cardoso MC. 2012. Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization. Nucleic Acids Res. 40:e176
21. Cavalli G, Misteli T. 2013. Functional implications of genome topology. Nat. Struct. Mol. Biol. 20:290-99
22. Cermak T, Doyle EL, Christian M, Wang L, Zhang Y, et al. 2011. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 39:e82
23. Chapman JR, Taylor MR, Boulton SJ. 2012. Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 47:497-510
24. Chari R, Mali P, Moosburner M, Church GM. 2015. Unraveling CRISPR-Cas9 genome engineering parameters via a library-on-library approach. Nat. Methods 12:823-26
25. Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, et al. 2013. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155:1479-91
26. Chen B, Hu J, Almeida R, Liu H, Balakrishnan S, et al. 2016. Expanding the CRISPR imaging toolset with Staphylococcus aureus Cas9 for simultaneous imaging of multiple genomic loci. Nucleic Acids Res. doi: 10.1093/nar/gkv1533
27. Chen B, Huang B. 2014. Imaging genomic elements in living cells using CRISPR/Cas9. Methods Enzymol. 546:337-54
28. Chen CY, Morris Q, Mitchell JA. 2012. Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features. BMC Genom. 13:152
29. Chen G, Mulla WA, Kucharavy A, Tsai HJ, Rubinstein B, et al. 2015. Targeting the adaptability of heterogeneous aneuploids. Cell 160:771-84
30. Cho SW, Kim S, Kim JM, Kim JS. 2013. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat. Biotechnol. 31:230-32
31. Choo Y, Sánchez-García I, Klug A. 1994. In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence. Nature 372:642-45
32. Cong L, Ran FA, Cox D, Lin S, Barretto R, et al. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science 339:819-23
33. Das T, Payer B, Cayouette M, Harris WA. 2003. In vivo time-lapse imaging of cell divisions during neurogenesis in the developing zebrafish retina. Neuron 37:597-609
34. de Wit E, de Laat W. 2012. A decade of 3C technologies: insights into nuclear organization. Genes Dev. 26:11-24
35. Dekker J. 2014. Two ways to fold the genome during the cell cycle: insights obtained with chromosome conformation capture. Epigenetics Chromatin 7:25
36. Dekker J, Marti-Renom MA, Mirny LA. 2013. Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nat. Rev. Genet. 14:390-403
37. Deng D, Yan C, Pan X, Mahfouz M, Wang J, et al. 2012. Structural basis for sequence-specific recognition of DNA by TAL effectors. Science 335:720-23
38. Ding Q, Regan SN, Xia Y, Oostrom LA, Cowan CA, Musunuru K. 2013. Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell 12:393-94
39. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, et al. 2012. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376-80
40. Doench JG, Hartenian E, Graham DB, Tothova Z, Hegde M, et al. 2014. Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation. Nat. Biotechnol. 32:1262-67
41. Duan Z, Andronescu M, Schutz K, McIlwain S, Kim YJ, et al. 2010. A three-dimensional model of the yeast genome. Nature 465:363-67
42. Essers J, van Cappellen WA, Theil AF, van Drunen E, Jaspers NG, et al. 2005. Dynamics of relative chromosome position during the cell cycle. Mol. Biol. Cell 16:769-75
43. Esvelt KM, Mali P, Braff JL, Moosburner M, Yaung SJ, Church GM. 2013. Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. Nat. Methods 10:1116-21
44. Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, et al. 2013. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat. Biotechnol. 31:822-26
45. Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK. 2014. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat. Biotechnol. 32:279-84
46. Gagnon JA, Valen E, Thyme SB, Huang P, Akhmetova L, et al. 2014. Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLOS ONE 9:e98186
47. Gasiunas G, Barrangou R, Horvath P, Siksnys V. 2012. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. PNAS 109:E2579-86
48. Gasser SM. 2002. Visualizing chromatin dynamics in interphase nuclei. Science 296:1412-16
49. Gerlich D, Beaudouin J, Kalbfuss B, Daigle N, Eils R, Ellenberg J. 2003. Global chromosome positions are transmitted through mitosis in mammalian cells. Cell 112:751-64
50. Gibcus JH, Dekker J. 2013. The hierarchy of the 3D genome. Mol. Cell 49:773-82
51. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, et al. 2014. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159:647-61
52. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, et al. 2013. CRISPR-mediated modular RNAguided regulation of transcription in eukaryotes. Cell 154:442-51
53. Giorgetti L, Galupa R, Nora EP, Piolot T, Lam F, et al. 2014. Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription. Cell 157:950-63
54. Green B, Bouchier C, Fairhead C, Craig NL, Cormack BP. 2012. Insertion site preference of Mu, Tn5, and Tn7 transposons. Mob. DNA 3:3
55. Guilinger JP, Thompson DB, Liu DR. 2014. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 32:577-82
56. Heintzman ND, Ren B. 2009. Finding distal regulatory elements in the human genome. Curr. Opin. Genet. Dev. 19:541-49
57. Holkers M, Maggio I, Liu J, Janssen JM, Miselli F, et al. 2013. Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res. 41:e63
58. Horvath P, Barrangou R. 2010. CRISPR/Cas, the immune system of bacteria and archaea. Science 327:167-70
59. Hou Z, Zhang Y, Propson NE, Howden SE, Chu LF, et al. 2013. Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. PNAS 110:15644-49
60. Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, et al. 2013. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31:827-32
61. Jiang F, Doudna JA. 2015. The structural biology of CRISPR-Cas systems. Curr. Opin. Struct. Biol. 30:100-11
62. Jiang F, Zhou K, Ma L, Gressel S, Doudna JA. 2015. A Cas9-guide RNA complex preorganized for target DNA recognition. Science 348:1477-81
63. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816-21
64. Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J. 2013. RNA-programmed genome editing in human cells. eLife 2:e00471
65. Kabadi AM, Ousterout DG, Hilton IB, Gersbach CA. 2014. Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector. Nucleic Acids Res. 42:e147
66. Kalhor R, Tjong H, Jayathilaka N, Alber F, Chen L. 2012. Genome architectures revealed by tethered chromosome conformation capture and population-based modeling. Nat. Biotechnol. 30:90-98
67. Kamiyama D, Sekine S, Barsi-Rhyne B, Hu J, Chen B, et al. 2016. Versatile protein tagging in cells with split fluorescent protein. Nat. Comm. 7:11046
68. Kanda T, Sullivan KF, Wahl GM. 1998. Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr. Biol. 8:377-85
69. Kim H, Kim JS. 2014. A guide to genome engineering with programmable nucleases. Nat. Rev. Genet. 15:321-34
70. Kim Y, Kweon J, Kim A, Chon JK, Yoo JY, et al. 2013. A library of TAL effector nucleases spanning the human genome. Nat. Biotechnol. 31:251-58
71. Kimura H, Cook PR. 2001. Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J. Cell Biol. 153:1341-53
72. Kleinstiver BP, Prew MS, Tsai SQ, Nguyen NT, Topkar VV, et al. 2015. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat. Biotechnol. 33:1293-98
73. Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, et al. 2015. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523:481-85
74. Klug A. 1993. Co-chairman's remarks: protein designs for the specific recognition of DNA. Gene 135:83-92
75. Knight SC, Xie L, Deng W, Guglielmi B, Witkowsky LB, et al. 2015. Dynamics of CRISPR-Cas9 genome interrogation in living cells. Science 350:823-26
76. Koike-Yusa H, Li Y, Tan E-P, Velasco-Herrera MDC, Yusa K. 2014. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat. Biotechnol. 32:267-73
77. Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, et al. 2015. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517:583-88
78. Kuscu C, Arslan S, Singh R, Thorpe J, Adli M. 2014. Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease. Nat. Biotechnol. 32:677-83
79. Lanctot C, Cheutin T, Cremer M, Cavalli G, Cremer T. 2007. Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat. Rev. Genet. 8:104-15
80. Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Yang JL, et al. 2014. Highly multiplexed subcellular RNA sequencing in situ. Science 343:1360-63
81. Lesterlin C, Ball G, Schermelleh L, Sherratt DJ. 2014. RecA bundles mediate homology pairing between distant sisters during DNA break repair. Nature 506:249-53
82. Li G, Sudlow G, Belmont AS. 1998. Interphase cell cycle dynamics of a late-replicating, heterochromatic homogeneously staining region: precise choreography of condensation/decondensation and nuclear positioning. J. Cell Biol. 140:975-89
83. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, et al. 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289-93
84. Lindhout BI, Fransz P, Tessadori F, Meckel T, Hooykaas PJ, van der Zaal BJ. 2007. Live cell imaging of repetitive DNA sequences via GFP-tagged polydactyl zinc finger proteins. Nucleic Acids Res. 35:e107
85. Lucas JS, Zhang Y, Dudko OK, Murre C. 2014. 3D trajectories adopted by coding and regulatory DNA elements: first-passage times for genomic interactions. Cell 158:339-52
86. Ma H, Naseri A, Reyes-Gutierrez P, Wolfe SA, Zhang S, Pederson T. 2015. Multicolor CRISPR labeling of chromosomal loci in human cells. PNAS 112:3002-7
87. Ma H, Reyes-Gutierrez P, Pederson T. 2013. Visualization of repetitive DNA sequences in human chromosomes with transcription activator-like effectors. PNAS 110:21048-53
88. Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK. 2013. CRISPR RNA-guided activation of endogenous human genes. Nat. Methods 10:977-79
89. Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, et al. 2008. Rapid "opensource" engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol. Cell 31:294-301
90. Mahfouz MM, Li L, Piatek M, Fang X, Mansour H, et al. 2012. Targeted transcriptional repression using a chimeric TALE-SRDX repressor protein. Plant Mol. Biol. 78:311-21
91. Maizels N. 2005. Immunoglobulin gene diversification. Annu. Rev. Genet. 39:23-46
92. Mak AN, Bradley P, Cernadas RA, Bogdanove AJ, Stoddard BL. 2012. The crystal structure of TAL effector PthXo1 bound to its DNA target. Science 335:716-19
93. Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M, et al. 2013. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol. 31:833-38
94. Mali P, Esvelt KM, Church GM. 2013. Cas9 as a versatile tool for engineering biology. Nat. Methods 10:957-63
95. Marini B, Kertesz-Farkas A, Ali H, Lucic B, Lisek K, et al. 2015. Nuclear architecture dictates HIV-1 integration site selection. Nature 521:227-31
96. Martin RM, Leonhardt H, Cardoso MC. 2005. DNA labeling in living cells. Cytom. A 67:45-52
97. Masui O, Bonnet I, Le Baccon P, Brito I, Pollex T, et al. 2011. Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation. Cell 145:447-58
98. Matzke AJ, Huettel B, van der Winden J, Matzke M. 2005. Use of two-color fluorescence-tagged transgenes to study interphase chromosomes in living plants. Plant Physiol. 139:1586-96
99. Miller J, McLachlan AD, Klug A. 1985. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 4:1609-14
100. Miller JC, Tan S, Qiao G, Barlow KA, Wang J, et al. 2011. A TALE nuclease architecture for efficient genome editing. Nat. Biotechnol. 29:143-48
101. Miyanari Y, Ziegler-Birling C, Torres-Padilla ME. 2013. Live visualization of chromatin dynamics with fluorescent TALEs. Nat. Struct. Mol. Biol. 20:1321-24
102. Mora-Bermúdez F, Ellenberg J. 2007. Measuring structural dynamics of chromosomes in living cells by fluorescence microscopy. Methods 41:158-67
103. Morbitzer R, Elsaesser J, Hausner J, Lahaye T. 2011. Assembly of custom TALE-type DNA binding domains by modular cloning. Nucleic Acids Res. 39:5790-99
104. Moscou MJ, Bogdanove AJ. 2009. A simple cipher governs DNA recognition by TAL effectors. Science 326:1501
105. Nagano T, Lubling Y, Stevens TJ, Schoenfelder S, Yaffe E, et al. 2013. Single-cell Hi-C reveals cell-tocell variability in chromosome structure. Nature 502:59-64
106. Naumova N, Imakaev M, Fudenberg G, Zhan Y, Lajoie BR, et al. 2013. Organization of the mitotic chromosome. Science 342:948-53
107. Nguyen DK, Disteche CM. 2006. Dosage compensation of the active X chromosome in mammals. Nat. Genet. 38:47-53
108. Nissim L, Perli SD, Fridkin A, Perez-Pinera P, Lu TK. 2014. Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells. Mol. Cell 54:698-710
109. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, et al. 2012. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381-85
110. 2 zinc finger proteins. Annu. Rev. Biochem. 70:313-40
111. Parada LA, McQueen PG, Munson PJ, Misteli T. 2002. Conservation of relative chromosome positioning in normal and cancer cells. Curr. Biol. 12:1692-97
112. Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA, Liu DR. 2013. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat. Biotechnol. 31:839-43
113. Pavletich NP, Pabo CO. 1991. Zinc finger-DNA recognition: crystal structure of aZif268-DNA complex at 2.1 A. Science 252:809-17
114. Pennacchio LA, Bickmore W, Dean A, Nobrega MA, Bejerano G. 2013. Enhancers: five essential questions. Nat. Rev. Genet. 14:288-95
115. Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM, et al. 2013. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat. Methods 10:973-76
116. Perez-Pinera P, Ousterout DG, Brunger JM, Farin AM, Glass KA, et al. 2013. Synergistic and tunable human gene activation by combinations of synthetic transcription factors. Nat. Methods 10:239-42
117. Petrie HT, Livak F, Burtrum D, Mazel S. 1995. T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. J. Exp. Med. 182:121-27
118. Porteus MH, Baltimore D. 2003. Chimeric nucleases stimulate gene targeting in human cells. Science 300:763
119. Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, et al. 2013. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152:1173-83
120. Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, et al. 2015. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520:186-91
121. Rao SSP, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, et al. 2014. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159:1665-80
122. Reyon D, Tsai SQ, Khayter C, Foden JA, Sander JD, Joung JK. 2012. FLASH assembly of TALENs for high-throughput genome editing. Nat. Biotechnol. 30:460-65
123. Robinett CC, Straight A, Li G, Willhelm C, Sudlow G, et al. 1996. In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition. J. Cell Biol. 135:1685-700
124. Roukos V, Voss TC, Schmidt CK, Lee S, Wangsa D, Misteli T. 2013. Spatial dynamics of chromosome translocations in living cells. Science 341:660-64
125. Saad H, Gallardo F, Dalvai M, Tanguy-le-Gac N, Lane D, Bystricky K. 2014. DNA dynamics during early double-strand break processing revealed by non-intrusive imaging of living cells. PLOS Genet. 10:e1004187
126. Sagai T, Amano T, Tamura M, Mizushina Y, Sumiyama K, Shiroishi T. 2009. A cluster of three longrange enhancers directs regional Shh expression in the epithelial linings. Development 136:1665-74
127. Sakabe NJ, Savic D, Nobrega MA. 2012. Transcriptional enhancers in development and disease. Genome Biol. 13:238
128. Sander JD, Joung JK. 2014. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol. 32:347-55
129. Schmid-Burgk JL, Schmidt T, Kaiser V, Honing K, Hornung V. 2013. A ligation-independent cloning technique for high-throughput assembly of transcription activator-like effector genes. Nat. Biotechnol. 31:76-81
130. Semenova E, Jore MM, Datsenko KA, Semenova A, Westra ER, et al. 2011. Interference by clustered regularly interspaced short palindromic repeat (CRISPR) RNA is governed by a seed sequence. PNAS 108:10098-103
131. Shachar S, Voss TC, Pegoraro G, Sciascia N, Misteli T. 2015. Identification of gene positioning factors using high-throughput imaging mapping. Cell 162:911-23
132. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, et al. 2014. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343:84-87
133. Shao S, Zhang W, Hu H, Xue B, Qin J, et al. 2016. Long-term dual-color tracking of genomic loci by modified sgRNAs of the CRISPR/Cas9 system. Nucleic Acids Res. doi: 10.1093/nar/gkw066
134. Siegel JJ, Amon A. 2012. New insights into the troubles of aneuploidy. Annu. Rev. Cell Dev. Biol. 28:189-214
135. Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, et al. 2007. Positional stability of single double-strand breaks in mammalian cells. Nat. Cell Biol. 9:675-82
136. Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA. 2005. Interchromosomal associations between alternatively expressed loci. Nature 435:637-45
137. Sternberg SH, Redding S, Jinek M, Greene EC, Doudna JA. 2014. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature 507:62-67
138. Streblow RC, Dafferner AJ, Nelson M, Fletcher M, West WW, et al. 2007. Imbalances of chromosomes 4, 9, and 12 are recurrent in the thecoma-fibroma group of ovarian stromal tumors. Cancer Genet. Cytogenet. 178:135-40
139. Strickfaden H, Zunhammer A, van Koningsbruggen S, Kohler D, Cremer T. 2010. 4D chromatin dynamics in cycling cells: Theodor Boveri's hypotheses revisited. Nucleus 1:284-97
140. Strukov YG, Belmont AS. 2009. Mitotic chromosome structure: reproducibility of folding and symmetry between sister chromatids. Biophys. J. 96:1617-28
141. Sun N, Zhao H. 2013. Transcription activator-like effector nucleases (TALENs): a highly efficient and versatile tool for genome editing. Biotechnol. Bioeng. 110:1811-21
142. Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD. 2014. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159:635-46
143. Terns MP, Terns RM. 2011. CRISPR-based adaptive immune systems. Curr. Opin. Microbiol. 14:321-27
144. Thanisch K, Schneider K, Morbitzer R, Solovei I, Lahaye T, et al. 2014. Targeting and tracing of specific DNA sequences with dTALEs in living cells. Nucleic Acids Res. 42:e38
145. Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V, et al. 2014. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat. Biotechnol. 32:569-76
146. Tsai SQ, Zheng Z, Nguyen NT, Liebers M, Topkar VV, et al. 2015. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat. Biotechnol. 33:187-97
147. Tupler R, Perini G, Green MR. 2001. Expressing the human genome. Nature 409:832-33
148. Tüzel E. 2011. Organelle dynamics: a tale of fusing nucleoli. Curr. Biol. 21:R395-97
149. Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, et al. 2005. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435:646-51
150. van Berkum NL, Lieberman-Aiden E, Williams L, Imakaev M, Gnirke A, et al. 2010. Hi-C: a method to study the three-dimensional architecture of genomes. J. Vis. Exp. 39:e1869
151. Vasuri F, Magrini E, Foschini MP, Eusebi V. 2008. Trisomy of chromosome 6 in Merkel cell carcinoma within lymph nodes. Virchows Arch. 452:559-63
152. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, et al. 2011. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120-24
153. Wang T, Wei JJ, Sabatini DM, Lander ES. 2014. Genetic screens in human cells using the CRISPR-Cas9 system. Science 343:80-84
154. Wiedenheft B, Sternberg SH, Doudna JA. 2012. RNA-guided genetic silencing systems in bacteria and archaea. Nature 482:331-38
155. Wiedenheft B, van Duijn E, Bultema JB, Waghmare SP, Zhou K, et al. 2011. RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions. PNAS 108:10092-27
156. Wu X, Scott DA, Kriz AJ, Chiu AC, Hsu PD, et al. 2014. Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. Nat. Biotechnol. 32:670-76
157. Yuan K, Shermoen AW, O'Farrell PH. 2014. Illuminating DNA replication during Drosophila development using TALE-lights. Curr. Biol. 24:R144-45
158. Zalatan JG, Lee ME, Almeida R, Gilbert LA, Whitehead EH, et al. 2015. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell 160:339-50
159. Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, et al. 2015. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163:759-71
160. Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, et al. 2015. Chromothripsis from DNA damage in micronuclei. Nature 522:179-84
161. Zhang F, Cong L, Lodato S, Kosuri S, Church GM, Arlotta P. 2011. Efficient construction of sequencespecific TAL effectors for modulating mammalian transcription. Nat. Biotechnol. 29:149-53
162. Zhang Y, Wong CH, Birnbaum RY, Li G, Favaro R, et al. 2013. Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations. Nature 504:306-10
163. Zhou Y, Zhu S, Cai C, Yuan P, Li C, et al. 2014. High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature 509:487-91
164. Zink D, Sadoni N, Stelzer E. 2003. Visualizing chromatin and chromosomes in living cells. Methods 29:42-50