Using transgenic reporter assays to functionally characterize enhancers in animals

Genomics

Volumn 106, Issue 3, 2015, Pages 185-192

  Kvon, Evgeny Z ^a  

^a LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

Author keywords

BAC transgenesis; Cis regulatory module; Enhancer; Enhancer trap; Regulatory genomics; Transgenic reporter; Transposon

Indexed keywords

TRANSCRIPTION FACTOR;

ASSAY; BACTERIAL ARTIFICIAL CHROMOSOME; BINDING SITE; CELL CULTURE; CHROMATIN IMMUNOPRECIPITATION; CRISPR CAS SYSTEM; DNA SEQUENCE; ENHANCER REGION; GENE EXPRESSION; GENE MAPPING; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; HIGH THROUGHPUT SEQUENCING; HISTONE MODIFICATION; HOMOLOGOUS RECOMBINATION; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; REPORTER GENE; REVIEW; TRANSGENIC REPORTER ASSAY; TRANSGENICS; TRANSPOSON; ANIMAL; DROSOPHILA; GENE EXPRESSION REGULATION; GENE TRANSFER; GENETICS; GENOMICS; MOUSE; TRANSGENIC ANIMAL;

ANIMALIA;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; DROSOPHILA; ENHANCER ELEMENTS, GENETIC; GENE EXPRESSION REGULATION; GENE TRANSFER TECHNIQUES; GENOMICS; MICE;

EID: 84939259288     PISSN: 08887543     EISSN: 10898646     Source Type: Journal    
DOI: 10.1016/j.ygeno.2015.06.007     Document Type: Review

References (139)

1. Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell 1981, 27:299-308.
2. Doyle H.J., Kraut R., Levine M.S. Spatial regulation of zerknüllt: a dorsal-ventral patterning gene in Drosophila. Genes Dev. 1989, 3:1518-1533. 10.1101/gad.3.10.1518.
3. Goto T., Macdonald P., Maniatis T. Early and late periodic patterns of even skipped expression are controlled by distinct regulatory elements that respond to different spatial cues. Cell 1989, 57:413-422.
4. Stanojevic D., Small S., Levine M.S. Regulation of a segmentation stripe by overlapping activators and repressors in the Drosophila embryo. Science 1991, 254:1385-1387.
5. Gillies S.D., Morrison S.L., Oi V.T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 1983, 33:717-728.
6. Müller F., Williams D.W., Kobolák J., Gauvry L., Goldspink G., Orbán L., et al. Activator effect of coinjected enhancers on the muscle-specific expression of promoters in zebrafish embryos. Mol. Reprod. Dev. 1997, 47:404-412. 10.1002/(SICI)1098-2795(199708)47:4<404::AID-MRD6>3.0.CO;2-O.
7. Yuh C.H., Bolouri H., Davidson E.H. Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene. Science 1998, 279:1896-1902.
8. Harafuji N., Keys D.N., Levine M.S. Genome-wide identification of tissue-specific enhancers in the Ciona tadpole. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:6802-6805. 10.1073/pnas.052024999.
9. Wenick A.S., Hobert O. Genomic cis-regulatory architecture and trans-acting regulators of a single interneuron-specific gene battery in C. elegans. Dev. Cell 2004, 6:757-770. 10.1016/j.devcel.2004.05.004.
10. Levine M. Transcriptional enhancers in animal development and evolution. Curr. Biol. 2010, 20:R754-R763. 10.1016/j.cub.2010.06.070.
11. Shlyueva D., Stampfel G., Stark A. Transcriptional enhancers: from properties to genome-wide predictions. Nat. Rev. Genet. 2014, 15:272-286. 10.1038/nrg3682.
12. Visel A., Rubin E.M., Pennacchio L.A. Genomic views of distant-acting enhancers. Nature 2009, 461:199-205. 10.1038/nature08451.
13. Lettice L.A., Heaney S.J.H., Purdie L.A., Li L., de Beer P., Oostra B.A., et al. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum. Mol. Genet. 2003, 12:1725-1735.
14. Carroll S.B. Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell 2008, 134:25-36. 10.1016/j.cell.2008.06.030.
15. Wray G.A. The evolutionary significance of cis-regulatory mutations. Nat. Rev. Genet. 2007, 8:206-216. 10.1038/nrg2063.
16. Lee T.I., Young R.A. Transcriptional regulation and its misregulation in disease. Cell 2013, 152:1237-1251. 10.1016/j.cell.2013.02.014.
17. Herz H.-M., Hu D., Shilatifard A. Enhancer malfunction in cancer. Mol. Cell 2014, 53:859-866. 10.1016/j.molcel.2014.02.033.
18. Rubin G.M., Spradling A.C. Genetic transformation of Drosophilawith transposable element vectors. Science 1982, 218:348-353.
19. Small S., Blair A., Levine M.S. Regulation of even-skipped stripe 2 in the Drosophila embryo. EMBO J. 1992, 11:4047-4057.
20. O'Kane C.J., Gehring W.J. Detection in situ of genomic regulatory elements in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 1987, 84:9123-9127.
21. Bothma J.P., Garcia H.G., Esposito E., Schlissel G., Gregor T., Levine M.S. Dynamic regulation of eve stripe 2 expression reveals transcriptional bursts in living Drosophila embryos. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:10598-10603. 10.1073/pnas.1410022111.
22. Kothary R., Clapoff S., Darling S., Perry M.D., Moran L.A., Rossant J. Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice. Development 1989, 105:707-714.
23. Chiocchetti A., Tolosano E., Hirsch E., Silengo L., Altruda F. Green fluorescent protein as a reporter of gene expression in transgenic mice. Biochim. Biophys. Acta 1997, 1352:193-202.
24. Suryamohan K., Halfon M.S. Identifying transcriptional cis-regulatory modules in animal genomes. Wiley Interdiscip. Rev. Dev. Biol. 2015, 4:59-84. 10.1002/wdev.168.
25. Graur D., Zheng Y., Price N., Azevedo R.B.R., Zufall R.A., Elhaik E. On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE. Genome Biol. Evol. 2013, 10.1093/gbe/evt028.
26. Eddy S.R. The C-value paradox, junk DNA and ENCODE. Curr. Biol. 2012, 22:R898-R899. 10.1016/j.cub.2012.10.002.
27. Doolittle W.F. Is junk DNA bunk? A critique of ENCODE. Proc. Natl. Acad. Sci. U. S. A. 2013, 10.1073/pnas.1221376110.
28. Sandmann T., Girardot C., Brehme M., Tongprasit W., Stolc V., Furlong E.E.M. A core transcriptional network for early mesoderm development in Drosophila melanogaster. Genes Dev. 2007, 21:436-449. 10.1101/gad.1509007.
29. Zeitlinger J., Zinzen R.P., Stark A., Kellis M., Zhang H., Young R.A., et al. Whole-genome ChIP-chip analysis of dorsal, twist, and snail suggests integration of diverse patterning processes in the Drosophila embryo. Genes Dev. 2007, 21:385-390. 10.1101/gad.1509607.
30. Bonn S., Zinzen R.P., Girardot C., Gustafson E.H., Perez-Gonzalez A., Delhomme N., et al. Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development. Nat. Genet. 2012, 44:148-156. 10.1038/ng.1064.
31. Zinzen R.P., Girardot C., Gagneur J., Braun M., Furlong E.E.M. Combinatorial binding predicts spatio-temporal cis-regulatory activity. Nature 2009, 462:65-70. 10.1038/nature08531.
32. Li X.-Y., MacArthur S., Bourgon R., Nix D., Pollard D.A., Iyer V.N., et al. Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. PLoS Biol. 2008, 6:e27. 10.1371/journal.pbio.0060027.
33. Visel A., Blow M.J., Li Z., Zhang T., Akiyama J.A., Holt A., et al. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 2009, 457:854-858. 10.1038/nature07730.
34. Nord A.S., Blow M.J., Attanasio C., Akiyama J.A., Holt A., Hosseini R., et al. Rapid and pervasive changes in genome-wide enhancer usage during mammalian development. Cell 2013, 155:1521-1531. 10.1016/j.cell.2013.11.033.
35. Crawford G.E., Holt I.E., Whittle J., Webb B.D., Tai D., Davis S., et al. Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Res. 2006, 16:123-131. 10.1101/gr.4074106.
36. Schones D.E., Cui K., Cuddapah S., Roh T.-Y., Barski A., Wang Z., et al. Dynamic regulation of nucleosome positioning in the human genome. Cell 2008, 132:887-898. 10.1016/j.cell.2008.02.022.
37. Buenrostro J.D., Giresi P.G., Zaba L.C., Chang H.Y., Greenleaf W.J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 2013, 10.1038/nmeth.2688.
38. Giresi P.G., Kim J., McDaniell R.M., Iyer V.R., Lieb J.D. FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Res. 2007, 17:877-885. 10.1101/gr.5533506.
39. modENCODE Consortium, Roy S., Ernst J., Kharchenko P.V., Kheradpour P., Negre N., et al. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 2010, 330:1787-1797. 10.1126/science.1198374.
40. Gerstein M.B., Lu Z.J., Van Nostrand E.L., Cheng C., Arshinoff B.I., Liu T., et al. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 2010, 10.1126/science.1196914.
41. Vierstra J., Rynes E., Sandstrom R., Zhang M., Canfield T., Hansen R.S., et al. Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution. Science 2014, 346:1007-1012. 10.1126/science.1246426.
42. Yue F., Cheng Y., Breschi A., Vierstra J., Wu W., Ryba T., et al. A comparative encyclopedia of DNA elements in the mouse genome. Nature 2014, 515:355-364. 10.1038/nature13992.
43. ENCODE Project Consortium, Bernstein B.E., Birney E., Dunham I., Green E.D., Gunter C., et al. An integrated encyclopedia of DNA elements in the human genome. Nature 2012, 489:57-74. 10.1038/nature11247.
44. Thurman R.E., Rynes E., Humbert R., Vierstra J., Maurano M.T., Haugen E., et al. The accessible chromatin landscape of the human genome. Nature 2012, 489:75-82. 10.1038/nature11232.
45. Stergachis A.B., Neph S., Reynolds A., Humbert R., Miller B., Paige S.L., et al. Developmental fate and cellular maturity encoded in human regulatory DNA landscapes. Cell 2013, 154:888-903. 10.1016/j.cell.2013.07.020.
46. de Wit E., de Laat W. A decade of 3C technologies: insights into nuclear organization. Genes Dev. 2012, 26:11-24. 10.1101/gad.179804.111.
47. Ghavi-Helm Y., Klein F.A., Pakozdi T., Ciglar L., Noordermeer D., Huber W., et al. Enhancer loops appear stable during development and are associated with paused polymerase. Nature 2014, 10.1038/nature13417.
48. Montavon T., Soshnikova N., Mascrez B., Joye E., Thevenet L., Splinter E., et al. A regulatory archipelago controls Hox genes transcription in digits. Cell 2011, 147:1132-1145. 10.1016/j.cell.2011.10.023.
49. He Q., Bardet A.F., Patton B., Purvis J., Johnston J., Paulson A., et al. High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species. Nat. Genet. 2011, 43:414-420. 10.1038/ng.808.
50. Heinz S., Benner C., Spann N., Bertolino E., Lin Y.C., Laslo P., et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 2010, 38:576-589. 10.1016/j.molcel.2010.05.004.
51. Fisher W.W., Li J.J., Hammonds A.S., Brown J.B., Pfeiffer B.D., Weiszmann R., et al. DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 2012, 10.1073/pnas.1209589110.
52. Kvon E.Z., Stampfel G., Yanez-Cuna J.O., Dickson B.J., Stark A. HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature. Genes Dev. 2012, 26:908-913. 10.1101/gad.188052.112.
53. Teytelman L., Thurtle D.M., Rine J., van Oudenaarden A. Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins. Proc. Natl. Acad. Sci. U. S. A. 2013, 10.1073/pnas.1316064110.
54. Heintzman N.D., Stuart R.K., Hon G., Fu Y., Ching C.W., Hawkins R.D., et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 2007, 39:311-318. 10.1038/ng1966.
55. Kwasnieski J.C., Fiore C., Chaudhari H.G., Cohen B.A. High-throughput functional testing of ENCODE segmentation predictions. Genome Res. 2014, 24:1595-1602. 10.1101/gr.173518.114.
56. Arnold C.D., Gerlach D., Stelzer C., Boryn L.M., Rath M., Stark A. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 2013, 10.1126/science.1232542.
57. Calo E., Wysocka J. Modification of enhancer chromatin: what, how, and why?. Mol. Cell 2013, 49:825-837. 10.1016/j.molcel.2013.01.038.
58. Williamson I., Berlivet S., Eskeland R., Boyle S., Illingworth R.S., Paquette D., et al. Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization. Genes Dev. 2014, 28:2778-2791. 10.1101/gad.251694.114.
59. Amano T., Sagai T., Tanabe H., Mizushina Y., Nakazawa H., Shiroishi T. Chromosomal dynamics at the Shh locus: limb bud-specific differential regulation of competence and active transcription. Dev. Cell 2009, 16:47-57. 10.1016/j.devcel.2008.11.011.
60. Schwarzer W., Spitz F. The architecture of gene expression: integrating dispersed cis-regulatory modules into coherent regulatory domains. Curr. Opin. Genet. Dev. 2014, 27:74-82. 10.1016/j.gde.2014.03.014.
61. Bickmore W.A. The spatial organization of the human genome. Annu. Rev. Genomics Hum. Genet. 2013, 14:67-84. 10.1146/annurev-genom-091212-153515.
62. Bickmore W.A., van Steensel B. Genome architecture: domain organization of interphase chromosomes. Cell 2013, 152:1270-1284. 10.1016/j.cell.2013.02.001.
63. Dixon J.R., Selvaraj S., Yue F., Kim A., Li Y., Shen Y., et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 2012, 485:376-380. 10.1038/nature11082.
64. Bellen H.J., O'Kane C.J., Wilson C., Grossniklaus U., Pearson R.K., Gehring W.J. P-element-mediated enhancer detection: a versatile method to study development in Drosophila. Genes Dev. 1989, 3:1288-1300.
65. Bier E., Vaessin H., Shepherd S., Lee K., McCall K., Barbel S., et al. Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. Genes Dev. 1989, 3:1273-1287.
66. Brand A.H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 1993, 118:401-415.
67. Ivics Z., Li M.A., Mátés L., Boeke J.D., Nagy A., Bradley A., et al. Transposon-mediated genome manipulation in vertebrates. Nat. Methods 2009, 6:415-422. 10.1038/nmeth.1332.
68. Kawakami K. Transposon tools and methods in zebrafish. Dev. Dyn. 2005, 234:244-254. 10.1002/dvdy.20516.
69. Ruf S., Symmons O., Uslu V.V., Dolle D., Hot C., Ettwiller L., et al. Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor. Nat. Genet. 2011, 43:379-386. 10.1038/ng.790.
70. Bellen H.J., Levis R.W., Liao G., He Y., Carlson J.W., Tsang G., et al. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 2004, 167:761-781. 10.1534/genetics.104.026427.
71. Marinić M., Aktas T., Ruf S., Spitz F. An integrated holo-enhancer unit defines tissue and gene specificity of the Fgf8 regulatory landscape. Dev. Cell 2013, 24:530-542. 10.1016/j.devcel.2013.01.025.
72. Anderson E., Devenney P.S., Hill R.E., Lettice L.A. Mapping the Shh long-range regulatory domain. Development 2014, 10.1242/dev.108480.
73. Visel A., Akiyama J.A., Shoukry M., Afzal V., Rubin E.M., Pennacchio L.A. Functional autonomy of distant-acting human enhancers. Genomics 2009, 93:509-513. 10.1016/j.ygeno.2009.02.002.
74. Sinzelle L., Vallin J., Coen L., Chesneau A., Pasquier D.Du., Pollet N., et al. Generation of trangenic Xenopus laevis using the Sleeping Beauty transposon system. Transgenic Res. 2006, 15:751-760. 10.1007/s11248-006-9014-6.
75. Sato Y., Kasai T., Nakagawa S., Tanabe K., Watanabe T., Kawakami K., et al. Stable integration and conditional expression of electroporated transgenes in chicken embryos. Dev. Biol. 2007, 305:616-624. 10.1016/j.ydbio.2007.01.043.
76. Dupuy A.J., Clark K., Carlson C.M., Fritz S., Davidson A.E., Markley K.M., et al. Mammalian germ-line transgenesis by transposition. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:4495-4499. 10.1073/pnas.062630599.
77. Pennacchio L.A., Ahituv N., Moses A.M., Prabhakar S., Nobrega M.A., Shoukry M., et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature 2006, 444:499-502. 10.1038/nature05295.
78. Visel A., Minovitsky S., Dubchak I., Pennacchio L.A. VISTA Enhancer Browser-a database of tissue-specific human enhancers. Nucleic Acids Res. 2007, 35:D88-D92. 10.1093/nar/gkl822.
79. Mello C.C., Kramer J.M., Stinchcomb D., Ambros V. Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991, 10:3959-3970.
80. Corbo J.C., Levine M.S., Zeller R.W. Characterization of a notochord-specific enhancer from the Brachyury promoter region of the ascidian, Ciona intestinalis. Development 1997, 124:589-602.
81. Uchikawa M. Enhancer analysis by chicken embryo electroporation with aid of genome comparison. Develop. Growth Differ. 2008, 50:467-474. 10.1111/j.1440-169X.2008.01028.x.
82. Keys D.N., Lee B.-I., Di Gregorio A., Harafuji N., Detter J.C., Wang M., et al. A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:679-683. 10.1073/pnas.0408952102.
83. Yang X.W., Gong S. An overview on the generation of BAC transgenic mice for neuroscience research. Curr. Protoc. Neurosci. 2005, (Chapter 5, Unit 5.20). 10.1002/0471142301.ns0520s31.
84. Dai J., Cui X., Zhu Z., Hu W. Non-homologous end joining plays a key role in transgene concatemer formation in transgenic zebrafish embryos. Int. J. Biol. Sci. 2010, 6:756-768.
85. Levis R., Hazelrigg T., Rubin G.M. Effects of genomic position on the expression of transduced copies of the white gene of Drosophila. Science 1985, 229:558-561.
86. Barolo S., Castro B., Posakony J.W. New Drosophila transgenic reporters: insulated P-element vectors expressing fast-maturing RFP. BioTechniques 2004, 36. (436-40-442).
87. Markstein M., Pitsouli C., Villalta C., Celniker S.E., Perrimon N. Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes. Nat. Genet. 2008, 40:476-483. 10.1038/ng.101.
88. Siegal M.L., Hartl D.L. Transgene coplacement and high efficiency site-specific recombination with the Cre/loxP system in Drosophila. Genetics 1996, 144:715-726.
89. Butler J.E., Kadonaga J.T. Enhancer-promoter specificity mediated by DPE or TATA core promoter motifs. Genes Dev. 2001, 15:2515-2519. 10.1101/gad.924301.
90. Thorpe H.M., Smith M.C. In vitro site-specific integration of bacteriophage DNA catalyzed by a recombinase of the resolvase/invertase family. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:5505-5510.
91. Groth A.C., Fish M., Nusse R., Calos M.P. Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31. Genetics 2004, 166:1775-1782.
92. Pfeiffer B.D., Jenett A., Hammonds A.S., Ngo T.-T.B., Misra S., Murphy C., et al. Tools for neuroanatomy and neurogenetics in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:9715-9720. 10.1073/pnas.0803697105.
93. Tasic B., Hippenmeyer S., Wang C., Gamboa M., Zong H., Chen-Tsai Y., et al. Site-specific integrase-mediated transgenesis in mice via pronuclear injection. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:7902-7907. 10.1073/pnas.1019507108.
94. Guenther C.A., Tasic B., Luo L., Bedell M.A., Kingsley D.M. A molecular basis for classic blond hair color in Europeans. Nat. Genet. 2014, 10.1038/ng.2991.
95. Bischof J., Maeda R.K., Hediger M., Karch F., Basler K. An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:3312-3317. 10.1073/pnas.0611511104.
96. Frøkjær-Jensen C., Davis M.W., Hopkins C.E., Newman B.J., Thummel J.M., Olesen S.-P., et al. Single-copy insertion of transgenes in Caenorhabditis elegans. Nat. Genet. 2008, 40:1375-1383. 10.1038/ng.248.
97. Doudna J.A., Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 2014, 346:1258096. 10.1126/science.1258096.
98. 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 2012, 337:816-821. 10.1126/science.1225829.
99. Yang H., Wang H., Shivalila C.S., Cheng A.W., Shi L., Jaenisch R. One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 2013, 154:1370-1379. 10.1016/j.cell.2013.08.022.
100. Gratz S.J., Ukken F.P., Rubinstein C.D., Thiede G., Donohue L.K., Cummings A.M., et al. Highly specific and efficient CRISPR/Cas9-catalyzed homology-directed repair in Drosophila. Genetics 2014, 196:961-971. 10.1534/genetics.113.160713.
101. Gallo S.M., Gerrard D.T., Miner D., Simich M., Des Soye B., Bergman C.M., et al. REDfly v3.0: toward a comprehensive database of transcriptional regulatory elements in Drosophila. Nucleic Acids Res. 2010, 10.1093/nar/gkq999.
102. Tassy O., Dauga D., Daian F., Sobral D., Robin F., Khoueiry P., et al. The ANISEED database: digital representation, formalization, and elucidation of a chordate developmental program. Genome Res. 2010, 10.1101/gr.108175.110.
103. Kvon E.Z., Kazmar T., Stampfel G., Yanez-Cuna J.O., Pagani M., Schernhuber K., et al. Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature 2014, 512:91-95. 10.1038/nature13395.
104. Jenett A., Rubin G.M., Ngo T.-T.B., Shepherd D., Murphy C., Dionne H., et al. A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012, 10.1016/j.celrep.2012.09.011.
105. Li H.-H., Kroll J.R., Lennox S.M., Ogundeyi O., Jeter J., Depasquale G., et al. A GAL4 driver resource for developmental and behavioral studies on the larval CNS of Drosophila. Cell Rep. 2014, 10.1016/j.celrep.2014.06.065.
106. Jory A., Estella C., Giorgianni M.W., Slattery M., Laverty T.R., Rubin G.M., et al. A survey of 6,300 genomic fragments for cis-regulatory activity in the imaginal discs of Drosophila melanogaster. Cell Rep. 2012, 10.1016/j.celrep.2012.09.010.
107. Manning L., Heckscher E.S., Purice M.D., Roberts J., Bennett A.L., Kroll J.R., et al. A resource for manipulating gene expression and analyzing cis-regulatory modules in the Drosophila CNS. Cell Rep. 2012, 10.1016/j.celrep.2012.09.009.
108. Phelps C.B., Brand A.H. Ectopic gene expression in Drosophila using GAL4 system. Methods 1998, 14:367-379. 10.1006/meth.1998.0592.
109. Visel A., Taher L., Girgis H., May D., Golonzhka O., Hoch R.V., et al. A high-resolution enhancer atlas of the developing telencephalon. Cell 2013, 152:895-908. 10.1016/j.cell.2012.12.041.
110. Yanez-Cuna J.O., Kvon E.Z., Stark A. Deciphering the transcriptional cis-regulatory code. Trends Genet. 2013, 29:11-22. 10.1016/j.tig.2012.09.007.
111. He X., Samee M.A.H., Blatti C., Sinha S. Thermodynamics-based models of transcriptional regulation by enhancers: the roles of synergistic activation, cooperative binding and short-range repression. PLoS Comput. Biol. 2010, 6. 10.1371/journal.pcbi.1000935.
112. Erwin G.D., Oksenberg N., Truty R.M., Kostka D., Murphy K.K., Ahituv N., et al. Integrating diverse datasets improves developmental enhancer prediction. PLoS Comput. Biol. 2014, 10:e1003677. 10.1371/journal.pcbi.1003677.
113. Zabidi M.A., Arnold C.D., Schernhuber K., Pagani M., Rath M., Frank O., et al. Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature 2014, 10.1038/nature13994.
114. Giraldo P., Montoliu L. Size matters: use of YACs, BACs and PACs in transgenic animals. Transgenic Res. 2001, 10:83-103.
115. Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., et al. The genome sequence of Drosophila melanogaster. Science 2000, 287:2185-2195.
116. Venken K.J.T., He Y., Hoskins R.A., Bellen H.J. P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 2006, 314:1747-1751. 10.1126/science.1134426.
117. Venken K., Carlson J., Schulze K., Pan H., He Y., Spokony R., et al. Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster. Nat. Methods 2009, 10.1038/nmeth.1331.
118. Fujioka M., Sun G., Jaynes J.B. The Drosophila eve insulator homie promotes eve expression and protects the adjacent gene from repression by polycomb spreading. PLoS Genet. 2013, 9:e1003883. 10.1371/journal.pgen.1003883.
119. Dunipace L., Saunders A., Ashe H.L., Stathopoulos A. Autoregulatory feedback controls sequential action of cis-regulatory modules at the brinker locus. Dev. Cell 2013, 26:536-543. 10.1016/j.devcel.2013.08.010.
120. Perry M.W., Boettiger A.N., Bothma J.P., Levine M.S. Shadow enhancers foster robustness of Drosophila gastrulation. Curr. Biol. 2010, 20:1562-1567. 10.1016/j.cub.2010.07.043.
121. Tsujimura T., Hosoya T., Kawamura S. A single enhancer regulating the differential expression of duplicated red-sensitive opsin genes in zebrafish. PLoS Genet. 2010, 6:e1001245. 10.1371/journal.pgen.1001245.
122. Zuniga A., Michos O., Spitz F., Haramis A.-P.G., Panman L., Galli A., et al. Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression. Genes Dev. 2004, 18:1553-1564. 10.1101/gad.299904.
123. Levine M.S., Cattoglio C., Tjian R. Looping back to leap forward: transcription enters a new era. Cell 2014, 157:13-25. 10.1016/j.cell.2014.02.009.
124. Smith R.P., Taher L., Patwardhan R.P., Kim M.J., Inoue F., Shendure J., et al. Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model. Nat. Genet. 2013, 10.1038/ng.2713.
125. Patwardhan R.P., Hiatt J.B., Witten D.M., Kim M.J., Smith R.P., May D., et al. Massively parallel functional dissection of mammalian enhancers in vivo. Nat. Biotechnol. 2012, 30:265-270. 10.1038/nbt.2136.
126. White M.A., Myers C.A., Corbo J.C., Cohen B.A. Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks. Proc. Natl. Acad. Sci. U. S. A. 2013, 10.1073/pnas.1307449110.
127. Melnikov A., Murugan A., Zhang X., Tesileanu T., Wang L., Rogov P., et al. Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay. Nat. Biotechnol. 2012, 30:271-277. 10.1038/nbt.2137.
128. Dickel D.E., Zhu Y., Nord A.S., Wylie J.N., Akiyama J.A., Afzal V., et al. Function-based identification of mammalian enhancers using site-specific integration. Nat. Methods 2014, 10.1038/nmeth.2886.
129. Murtha M., Tokcaer-Keskin Z., Tang Z., Strino F., Chen X., Wang Y., et al. FIREWACh: high-throughput functional detection of transcriptional regulatory modules in mammalian cells. Nat. Methods 2014, 10.1038/nmeth.2885.
130. Gisselbrecht S.S., Barrera L.A., Porsch M., Aboukhalil A., Estep P.W., Vedenko A., et al. Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos. Nat. Methods 2013, 10:774-780. 10.1038/nmeth.2558.
131. Ahituv N., Zhu Y., Visel A., Holt A., Afzal V., Pennacchio L.A., et al. Deletion of ultraconserved elements yields viable mice. PLoS Biol. 2007, 5:e234. 10.1371/journal.pbio.0050234.
132. Sagai T., Hosoya M., Mizushina Y., Tamura M., Shiroishi T. Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb. Development 2005, 132:797-803. 10.1242/dev.01613.
133. Attanasio C., Nord A.S., Zhu Y., Blow M.J., Li Z., Liberton D.K., et al. Fine tuning of craniofacial morphology by distant-acting enhancers. Science 2013, 342:1241006. 10.1126/science.1241006.
134. Poorey K., Viswanathan R., Carver M.N., Karpova T.S., Cirimotich S.M., McNally J.G., et al. Measuring chromatin interaction dynamics on the second time scale at single-copy genes. Science. 2013, 342:369-372. 10.1126/science.1242369.
135. Bronson S.K., Plaehn E.G., Kluckman K.D., Hagaman J.R., Maeda N., Smithies O. Single-copy transgenic mice with chosen-site integration. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:9067-9072.
136. Guillot P.V., Liu L., Kuivenhoven J.A., Guan J., Rosenberg R.D., Aird W.C. Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression. Physiol. Genomics. 2000, 2:77-83.
137. Liu J., Yuan L., Molema G., Regan E., Janes L., Beeler D., et al. Vascular bed-specific regulation of the von Willebrand factor promoter in the heart and skeletal muscle. Blood. 2011, 117:342-351. 10.1182/blood-2010-06-287987.
138. Lucas T., Ferraro T., Roelens B., De Las Heras Chanes J., Walczak A.M., Coppey M. Live Imaging of Bicoid-Dependent Transcription in Drosophila Embryos. Curr. Biol. 2013, 10.1016/j.cub.2013.08.053.
139. Garcia H.G., Tikhonov M., Lin A., Gregor T. Quantitative Imaging of Transcription in Living Drosophila Embryos Links Polymerase Activity to Patterning. Curr. Biol. 2013, 10.1016/j.cub.2013.08.054.