Identifying transcriptional cis-regulatory modules in animal genomes

Wiley Interdisciplinary Reviews: Developmental Biology

Volumn 4, Issue 2, 2015, Pages 59-84

  Suryamohan, Kushal ^a,b   Halfon, Marc S ^a,b,c  

^a UNIVERSITY AT BUFFALO   (United States)

^b UNIVERSITY AT BUFFALO   (United States)

^c ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CIS ACTING ELEMENT; TRANSCRIPTION FACTOR;

ARTICLE; BINDING SITE; CELL DIFFERENTIATION; CELL FATE; CHROMATIN ASSEMBLY AND DISASSEMBLY; CHROMATIN IMMUNOPRECIPITATION; GENE EXPRESSION PROFILING; GENE SEQUENCE; GENOME; GENOMICS; NONHUMAN; NUCLEOSOME; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN PROCESSING; SIGNAL TRANSDUCTION; TRANSCRIPTION ELONGATION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; TRANSCRIPTION TERMINATION; ANIMAL; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; REGULATORY SEQUENCE; REPORTER GENE;

ANIMALIA;

ANIMALS; BINDING SITES; GENES, REPORTER; GENOME; REGULATORY SEQUENCES, NUCLEIC ACID; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84923125972     PISSN: 17597684     EISSN: 17597692     Source Type: Journal    
DOI: 10.1002/wdev.168     Document Type: Article

References (193)

1. Pick L, Heffer A. Hox gene evolution: multiple mechanisms contributing to evolutionary novelties. Ann N Y Acad Sci 2012, 1256:15-32.
2. Smith E, Shilatifard A. Enhancer biology and enhanceropathies. Nat Struct Mol Biol 2014, 21:210-219.
3. Bulger M, Groudine M. Functional and mechanistic diversity of distal transcription enhancers. Cell 2011, 144:327-339.
4. Maston GA, Landt SG, Snyder M, Green MR. Characterization of enhancer function from genome-wide analyses. Annu Rev Genomics Hum Genet 2012, 13:29-57.
5. Ong CT, Corces VG. Enhancers: emerging roles in cell fate specification. EMBO Rep 2012, 13:423-430.
6. Spitz F, Furlong EE. Transcription factors: from enhancer binding to developmental control. Nat Rev Genet 2012, 13:613-626.
7. Schaffner W. Enhancer. In: Encyclopedia of Molecular Biology. John Wiley & Sons; 2002. doi:10.1002/047120918X.emb0478.
8. Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet 2006, 7:29-59.
9. Weake VM, Workman JL. Inducible gene expression: diverse regulatory mechanisms. Nat Rev Genet 2010, 11:426-437.
10. Calo E, Wysocka J. Modification of enhancer chromatin: what, how, and why? Mol Cell 2013, 49:825-837.
11. Li L, Zhu Q, He X, Sinha S, Halfon MS. Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses. Genome Biol 2007, 8:R101.
12. Lam MT, Li W, Rosenfeld MG, Glass CK. Enhancer RNAs and regulated transcriptional programs. Trends Biochem Sci 2014, 39:170-182.
13. Mousavi K, Zare H, Koulnis M, Sartorelli V. The emerging roles of eRNAs in transcriptional regulatory networks. RNA Biol 2014, 11:106-110.
14. Visel A, Minovitsky S, Dubchak I, Pennacchio LA. VISTA Enhancer Browser-a database of tissue-specific human enhancers. Nucleic Acids Res 2007, 35:D88-D92.
15. Bajic VB, Tan SL, Suzuki Y, Sugano S. Promoter prediction analysis on the whole human genome. Nat Biotechnol 2004, 22:1467-1473.
16. Wang Z, Chen Y, Li Y. A brief review of computational gene prediction methods. Genomics Proteomics Bioinformatics 2004, 2:216-221.
17. Zhu LJ, Christensen RG, Kazemian M, Hull CJ, Enuameh MS, Basciotta MD, Brasefield JA, Zhu C, Asriyan Y, Lapointe DS, et al. FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system. Nucleic Acids Res 2011, 39:D111-D117.
18. D'Haeseleer P. What are DNA sequence motifs? Nat Biotechnol 2006, 24:423-425.
19. Schneider TD, Stephens RM. Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 1990, 18:6097-6100.
20. Hertz GZ, Stormo GD. Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics 1999, 15:563-577.
21. Stormo GD. DNA binding sites: representation and discovery. Bioinformatics 2000, 16:16-23.
22. Zambelli F, Pesole G, Pavesi G. Motif discovery and transcription factor binding sites before and after the next-generation sequencing era. Brief Bioinform 2013, 14:225-237.
23. Stormo GD. Modeling the specificity of protein-DNA interactions. Cold Spring Harb Symp Quant Biol 2013, 1:115-130.
24. GuhaThakurta D. Computational identification of transcriptional regulatory elements in DNA sequence. Nucleic Acids Res 2006, 34:3585-3598. doi:10.1093/nar/gkl372.
25. Pavesi G, Mauri G, Pesole G. In silico representation and discovery of transcription factor binding sites. Brief Bioinform 2004, 5:217-236.
26. Jolma A, Taipale J. Methods for analysis of transcription factor DNA-binding specificity in vitro. Subcell Biochem 2011, 52:155-173.
27. MacIsaac KD, Fraenkel E. Practical strategies for discovering regulatory DNA sequence motifs. PLoS Comput Biol 2006, 2:e36.
28. Parker DS, White MA, Ramos AI, Cohen BA, Barolo S. The cis-regulatory logic of Hedgehog gradient responses: key roles for gli binding affinity, competition, and cooperativity. Sci Signal 2011, 4:ra38.
29. Swanson CI, Schwimmer DB, Barolo S. Rapid evolutionary rewiring of a structurally constrained eye enhancer. Curr Biol 2011, 21:1186-1196.
30. John S, Marais R, Child R, Light Y, Leonard WJ. Importance of low affinity Elf-1 sites in the regulation of lymphoid-specific inducible gene expression. J Exp Med 1996, 183:743-750.
31. Tanay A. Extensive low-affinity transcriptional interactions in the yeast genome. Genome Res 2006, 16:962-972.
32. Jaeger SA, Chan ET, Berger MF, Stottmann R, Hughes TR, Bulyk ML. Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites. Genomics 2010, 95:185-195.
33. Weirauch MT, Cote A, Norel R, Annala M, Zhao Y, Riley TR, Saez-Rodriguez J, Cokelaer T, Vedenko A, Talukder S, et al. Evaluation of methods for modeling transcription factor sequence specificity. Nat Biotechnol 2013, 31:126-134.
34. Maerkl SJ, Quake SR. A systems approach to measuring the binding energy landscapes of transcription factors. Science 2007, 315:233-237.
35. Gubelmann C, Waszak SM, Isakova A, Holcombe W, Hens K, Iagovitina A, Feuz JD, Raghav SK, Simicevic J, Deplancke B. A yeast one-hybrid and microfluidics-based pipeline to map mammalian gene regulatory networks. Mol Syst Biol 2013, 9:682.
36. Hens K, Feuz JD, Isakova A, Iagovitina A, Massouras A, Bryois J, Callaerts P, Celniker SE, Deplancke B. Automated protein-DNA interaction screening of Drosophila regulatory elements. Nat Methods 2011, 8:1065-1070.
37. Slattery M, Riley T, Liu P, Abe N, Gomez-Alcala P, Dror I, Zhou T, Rohs R, Honig B, Bussemaker HJ, et al. Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins. Cell 2011, 147:1270-1282.
38. Jolma A, Kivioja T, Toivonen J, Cheng L, Wei G, Enge M, Taipale M, Vaquerizas JM, Yan J, Sillanpaa MJ, et al. Multiplexed massively parallel SELEX for characterization of human transcription factor binding specificities. Genome Res 2010, 20:861-873.
39. Berger MF, Philippakis AA, Qureshi AM, He FS, Estep PW 3rd, Bulyk ML. Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities. Nat Biotechnol 2006, 24:1429-1435.
40. Noyes MB, Meng X, Wakabayashi A, Sinha S, Brodsky MH, Wolfe SA. A systematic characterization of factors that regulate Drosophila segmentation via a bacterial one-hybrid system. Nucleic Acids Res 2008, 36:2547-2560.
41. Buck MJ, Lieb JD. ChIP-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. Genomics 2004, 83:349-360.
42. Mardis ER. ChIP-seq: welcome to the new frontier. Nat Methods 2007, 4:613-614.
43. van Steensel B, Henikoff S. Identification of in vivo DNA targets of chromatin proteins using tethered dam methyltransferase. Nat Biotechnol 2000, 18:424-428.
44. Rhee HS, Pugh BF. Comprehensive genome-wide protein-DNA interactions detected at single-nucleotide resolution. Cell 2011, 147:1408-1419.
45. He Q, Johnston J, Zeitlinger J. A novel ChIP-exo method reveals genome-wide in vivo transcription factor binding footprints influenced by local DNA sequence. Nat Biotechnol. In press.
46. Mathelier A, Zhao X, Zhang AW, Parcy F, Worsley-Hunt R, Arenillas DJ, Buchman S, Chen CY, Chou A, Ienasescu H, et al. JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles. Nucleic Acids Res 2014, 42:D142-D147.
47. Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Reuter I, Chekmenev D, Krull M, Hornischer K, et al. TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res 2006, 34:D108-D110.
48. Robasky K, Bulyk ML. UniPROBE, update 2011: expanded content and search tools in the online database of protein-binding microarray data on protein-DNA interactions. Nucleic Acids Res 2011, 39:D124-D128.
49. Fisher WW, Li JJ, Hammonds AS, Brown JB, Pfeiffer BD, Weiszmann R, MacArthur S, Thomas S, Stamatoyannopoulos JA, Eisen MB, et al. DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila. Proc Natl Acad Sci USA 2012, 109:21330-21335.
50. Wasserman WW, Sandelin A. Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet 2004, 5:276-287.
51. Banerji J, Rusconi S, Schaffner W. Expression of a β-globin gene is enhanced by remote SV40 DNA sequences. Cell 1981, 27:299-308.
52. Shlyueva D, Stampfel G, Stark A. Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet 2014, 15:272-286.
53. Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 2005, 15:1034-1050.
54. Carroll SB, Grenier JK, Weatherbee SD. From DNA to Diversity : Molecular Genetics and the Evolution of Animal Design. 2nd ed. Malden, MA: Blackwell Publishing; 2005.
55. Davidson EH. The Regulatory Genome : Gene Regulatory Networks in Development and Evolution. Burlington, MA/San Diego, CA: Academic Press; 2006.
56. Barolo S, Posakony JW. Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev 2002, 16:1167-1181.
57. Halfon MS, Carmena A, Gisselbrecht S, Sackerson CM, Jimenez F, Baylies MK, Michelson AM. Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors. Cell 2000, 103:63-74.
58. Mann RS, Carroll SB. Molecular mechanisms of selector gene function and evolution. Curr Opin Genet Dev 2002, 12:592-600.
59. Britten RJ, Davidson EH. Gene regulation for higher cells: a theory. Science 1969, 165:349-357.
60. Ford E, Thanos D. The transcriptional code of human IFN-β gene expression. Biochim Biophys Acta 2010, 1799:328-336.
61. Arnosti DN, Kulkarni MM. Transcriptional enhancers: intelligent enhanceosomes or flexible billboards? J Cell Biochem 2005, 94:890-898.
62. Liu F, Posakony JW. Role of architecture in the function and specificity of two Notch-regulated transcriptional enhancer modules. PLoS Genet 2012, 8:e1002796.
63. Zeitlinger J, Zinzen RP, Stark A, Kellis M, Zhang H, Young RA, Levine M. 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.
64. Zinzen RP, Girardot C, Gagneur J, Braun M, Furlong EE. Combinatorial binding predicts spatio-temporal cis-regulatory activity. Nature 2009, 462:65-70.
65. Cheng Y, King DC, Dore LC, Zhang X, Zhou Y, Zhang Y, Dorman C, Abebe D, Kumar SA, Chiaromonte F, et al. Transcriptional enhancement by GATA1-occupied DNA segments is strongly associated with evolutionary constraint on the binding site motif. Genome Res 2008, 18:1896-1905.
66. Negre N, Brown CD, Ma L, Bristow CA, Miller SW, Wagner U, Kheradpour P, Eaton ML, Loriaux P, Sealfon R, et al. A cis-regulatory map of the Drosophila genome. Nature 2011, 471:527-531.
67. MacArthur S, Li XY, Li J, Brown JB, Chu HC, Zeng L, Grondona BP, Hechmer A, Simirenko L, Keranen SV, et al. Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biol 2009, 10:R80.
68. Moorman C, Sun LV, Wang J, de Wit E, Talhout W, Ward LD, Greil F, Lu XJ, White KP, Bussemaker HJ, et al. Hotspots of transcription factor colocalization in the genome of Drosophila melanogaster. Proc Natl Acad Sci USA 2006, 103:12027-12032.
69. Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, et al. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 2010, 330:1775-1787.
70. Yip KY, Cheng C, Bhardwaj N, Brown JB, Leng J, Kundaje A, Rozowsky J, Birney E, Bickel P, Snyder M, et al. Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription-related factors. Genome Biol 2012, 13:R48.
71. Kvon EZ, Stampfel G, Yanez-Cuna JO, Dickson BJ, Stark A. HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature. Genes Dev 2012, 26:908-913.
72. Li XY, MacArthur S, Bourgon R, Nix D, Pollard DA, Iyer VN, Hechmer A, Simirenko L, Stapleton M, Luengo Hendriks CL, et al. Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. PLoS Biol 2008, 6:e27.
73. Cao Y, Yao Z, Sarkar D, Lawrence M, Sanchez GJ, Parker MH, MacQuarrie KL, Davison J, Morgan MT, Ruzzo WL, et al. Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming. Dev Cell 2010, 18:662-674.
74. Park D, Lee Y, Bhupindersingh G, Iyer VR. Widespread misinterpretable ChIP-seq bias in yeast. PLoS One 2013, 8:e83506.
75. Teytelman L, Thurtle DM, Rine J, van Oudenaarden A. Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins. Proc Natl Acad Sci USA 2013, 110:18602-18607.
76. Halfon MS, Zhu Q, Brennan ER, Zhou Y. Erroneous attribution of relevant transcription factor binding sites despite successful prediction of cis-regulatory modules. BMC Genomics 2011, 12:578.
77. Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, et al. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 2009, 459:108-112.
78. Visel A, Blow MJ, Li Z, Zhang T, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Chen F, et al. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 2009, 457:854-858.
79. Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J. A unique chromatin signature uncovers early developmental enhancers in humans. Nature 2011, 470:279-283.
80. Blow MJ, McCulley DJ, Li Z, Zhang T, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Chen F, et al. ChIP-Seq identification of weakly conserved heart enhancers. Nat Genet 2010, 42:806-810.
81. May D, Blow MJ, Kaplan T, McCulley DJ, Jensen BC, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, et al. Large-scale discovery of enhancers from human heart tissue. Nat Genet 2012, 44:89-93.
82. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA, Frampton GM, Sharp PA, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci USA 2010, 107:21931-21936.
83. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 2007, 39:311-318.
84. modEncode Consortium, Roy S, Ernst J, Kharchenko PV, Kheradpour P, Negre N, Eaton ML, Landolin JM, Bristow CA, Ma L, et al. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 2010, 330:1787-1797.
85. Encode Project Consortium, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M. An integrated encyclopedia of DNA elements in the human genome. Nature 2012, 489:57-74.
86. Shen Y, Yue F, McCleary DF, Ye Z, Edsall L, Kuan S, Wagner U, Dixon J, Lee L, Lobanenkov VV, et al. A map of the cis-regulatory sequences in the mouse genome. Nature 2012, 488:116-120.
87. Bernstein BE, Stamatoyannopoulos JA, Costello JF, Ren B, Milosavljevic A, Meissner A, Kellis M, Marra MA, Beaudet AL, Ecker JR, et al. The NIH Roadmap Epigenomics Mapping Consortium. Nat Biotechnol 2010, 28:1045-1048.
88. Bonn S, Zinzen RP, Girardot C, Gustafson EH, Perez-Gonzalez A, Delhomme N, Ghavi-Helm Y, Wilczynski B, Riddell A, Furlong EE. Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development. Nat Genet 2012, 44:148-156.
89. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 2008, 40:897-903.
90. Ernst J, Kellis M. ChromHMM: automating chromatin-state discovery and characterization. Nat Methods 2012, 9:215-216.
91. Hoffman MM, Buske OJ, Wang J, Weng Z, Bilmes JA, Noble WS. Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nat Methods 2012, 9:473-476.
92. Kwasnieski JC, Fiore C, Chaudhari HG, Cohen BA. High-throughput functional testing of ENCODE segmentation predictions. Genome Res 2014, 24:1595-1602.
93. Kantorovitz MR, Kazemian M, Kinston S, Miranda-Saavedra D, Zhu Q, Robinson GE, Gottgens B, Halfon MS, Sinha S. Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse. Dev Cell 2009, 17:568-579.
94. Narlikar L, Sakabe NJ, Blanski AA, Arimura FE, Westlund JM, Nobrega MA, Ovcharenko I. Genome-wide discovery of human heart enhancers. Genome Res 2010, 20:381-392.
95. Bell O, Tiwari VK, Thoma NH, Schubeler D. Determinants and dynamics of genome accessibility. Nat Rev Genet 2011, 12:554-564.
96. Zaret KS, Carroll JS. Pioneer transcription factors: establishing competence for gene expression. Genes Dev 2011, 25:2227-2241.
97. Gross DS, Garrard WT. Nuclease hypersensitive sites in chromatin. Annu Rev Biochem 1988, 57:159-197.
98. Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS, Crawford GE. High-resolution mapping and characterization of open chromatin across the genome. Cell 2008, 132:311-322.
99. Hesselberth JR, Chen X, Zhang Z, Sabo PJ, Sandstrom R, Reynolds AP, Thurman RE, Neph S, Kuehn MS, Noble WS, et al. Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nat Methods 2009, 6:283-289.
100. Giresi PG, Kim J, McDaniell RM, Iyer VR, Lieb JD. FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Res 2007, 17:877-885.
101. Giresi PG, Lieb JD. Isolation of active regulatory elements from eukaryotic chromatin using FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements). Methods 2009, 48:233-239.
102. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods 2013, 10:1213-1218.
103. Adey A, Morrison HG, Asan, Xun X, Kitzman JO, Turner EH, Stackhouse B, MacKenzie AP, Caruccio NC, Zhang X, et al. Rapid, low-input, low-bias construction of shotgun fragment libraries by high-density in vitro transposition. Genome Biol 2010, 11:R119.
104. Kwasnieski JC, Mogno I, Myers CA, Corbo JC, Cohen BA. Complex effects of nucleotide variants in a mammalian cis-regulatory element. Proc Natl Acad Sci USA 2012, 109:19498-19503.
105. Nam J, Davidson EH. Barcoded DNA-tag reporters for multiplex cis-regulatory analysis. PLoS One 2012, 7:e35934.
106. Patwardhan RP, Hiatt JB, Witten DM, Kim MJ, Smith RP, May D, Lee C, Andrie JM, Lee SI, Cooper GM, et al. Massively parallel functional dissection of mammalian enhancers in vivo. Nat Biotechnol 2012, 30:265-270.
107. Melnikov A, Murugan A, Zhang X, Tesileanu T, Wang L, Rogov P, Feizi S, Gnirke A, Callan CG Jr, Kinney JB, et al. Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay. Nat Biotechnol 2012, 30:271-277.
108. Sharon E, Kalma Y, Sharp A, Raveh-Sadka T, Levo M, Zeevi D, Keren L, Yakhini Z, Weinberger A, Segal E. Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters. Nat Biotechnol 2012, 30:521-530.
109. White MA, Myers CA, Corbo JC, Cohen BA. Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks. Proc Natl Acad Sci USA 2013, 110:11952-11957.
110. Dickel DE, Zhu Y, Nord AS, Wylie JN, Akiyama JA, Afzal V, Plajzer-Frick I, Kirkpatrick A, Gottgens B, Bruneau BG, et al. Function-based identification of mammalian enhancers using site-specific integration. Nat Methods 2014, 11:566-571.
111. Murtha M, Tokcaer-Keskin Z, Tang Z, Strino F, Chen X, Wang Y, Xi X, Basilico C, Brown S, Bonneau R, et al. FIREWACh: high-throughput functional detection of transcriptional regulatory modules in mammalian cells. Nat Methods 2014, 11:559-565.
112. Gisselbrecht SS, Barrera LA, Porsch M, Aboukhalil A, Estep PW 3rd, Vedenko A, Palagi A, Kim Y, Zhu X, Busser BW, et al. Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos. Nat Methods 2013, 10:774-780.
113. Arnold CD, Gerlach D, Stelzer C, Boryn LM, Rath M, Stark A. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 2013, 339:1074-1077.
114. Aerts S. Computational strategies for the genome-wide identification of cis-regulatory elements and transcriptional targets. Curr Top Dev Biol 2012, 98:121-145.
115. Haeussler M, Joly JS. When needles look like hay: how to find tissue-specific enhancers in model organism genomes. Dev Biol 2011, 350:239-254.
116. Van Loo P, Marynen P. Computational methods for the detection of cis-regulatory modules. Brief Bioinform 2009, 10:509-524.
117. Miller W, Makova KD, Nekrutenko A, Hardison RC. Comparative genomics. Annu Rev Genomics Hum Genet 2004, 5:15-56.
118. Hardison RC. Conserved noncoding sequences are reliable guides to regulatory elements. Trends Genet 2000, 16:369-372.
119. Arnold CD, Gerlach D, Spies D, Matts JA, Sytnikova YA, Pagani M, Lau NC, Stark A. Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution. Nat Genet 2014, 46:685-692.
120. Su J, Teichmann SA, Down TA. Assessing computational methods of cis-regulatory module prediction. PLoS Comput Biol 2010, 6:e1001020.
121. Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM, Frazer KA. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 2000, 288:136-140.
122. Johnson DS, Davidson B, Brown CD, Smith WC, Sidow A. Noncoding regulatory sequences of Ciona exhibit strong correspondence between evolutionary constraint and functional importance. Genome Res 2004, 14:2448-2456.
123. Nobrega MA, Ovcharenko I, Afzal V, Rubin EM. Scanning human gene deserts for long-range enhancers. Science 2003, 302:413.
124. Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature 2006, 444:499-502.
125. Shin JT, Priest JR, Ovcharenko I, Ronco A, Moore RK, Burns CG, MacRae CA. Human-zebrafish non-coding conserved elements act in vivo to regulate transcription. Nucleic Acids Res 2005, 33:5437-5445.
126. Woolfe A, Goodson M, Goode DK, Snell P, McEwen GK, Vavouri T, Smith SF, North P, Callaway H, Kelly K, et al. Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol 2005, 3:e7.
127. Attanasio C, Reymond A, Humbert R, Lyle R, Kuehn MS, Neph S, Sabo PJ, Goldy J, Weaver M, Haydock A, et al. Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells. Genome Biol 2008, 9:R168.
128. King DC, Taylor J, Zhang Y, Cheng Y, Lawson HA, Martin J, ENCODE Groups for Transcriptional Regulation and Multispecies Sequence Analysis, Chiaromonte F, Miller W, Hardison RC. Finding cis-regulatory elements using comparative genomics: some lessons from ENCODE data. Genome Res 2007, 17:775-786. doi:10.1101/gr.5592107.
129. Hardison RC, Taylor J. Genomic approaches towards finding cis-regulatory modules in animals. Nat Rev Genet 2012, 13:469-483.
130. Rubinstein M, de Souza FS. Evolution of transcriptional enhancers and animal diversity. Philos Trans R Soc Lond B Biol Sci 2013, 368:20130017.
131. Junion G, Spivakov M, Girardot C, Braun M, Gustafson EH, Birney E, Furlong EE. A transcription factor collective defines cardiac cell fate and reflects lineage history. Cell 2012, 148:473-486.
132. Ludwig MZ, Bergman C, Patel NH, Kreitman M. Evidence for stabilizing selection in a eukaryotic enhancer element. Nature 2000, 403:564-567.
133. Vinga S, Almeida J. Alignment-free sequence comparison-a review. Bioinformatics 2003, 19:513-523.
134. Wasserman WW, Fickett JW. Identification of regulatory regions which confer muscle-specific gene expression. J Mol Biol 1998, 278:167-181.
135. Berman BP, Nibu Y, Pfeiffer BD, Tomancak P, Celniker SE, Levine M, Rubin GM, Eisen MB. Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome. Proc Natl Acad Sci USA 2002, 99:757-762.
136. Halfon MS, Grad Y, Church GM, Michelson AM. Computation-based discovery of related transcriptional regulatory modules and motifs using an experimentally validated combinatorial model. Genome Res 2002, 12:1019-1028.
137. Markstein M, Markstein P, Markstein V, Levine MS. Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the Drosophila embryo. Proc Natl Acad Sci USA 2002, 99:763-768.
138. Rebeiz M, Reeves NL, Posakony JW. SCORE: a computational approach to the identification of cis-regulatory modules and target genes in whole-genome sequence data. Site clustering over random expectation. Proc Natl Acad Sci USA 2002, 99:9888-9893.
139. Rajewsky N, Vergassola M, Gaul U, Siggia ED. Computational detection of genomic cis-regulatory modules applied to body patterning in the early Drosophila embryo. BMC Bioinformatics 2002, 3:30.
140. Berman BP, Pfeiffer BD, Laverty TR, Salzberg SL, Rubin GM, Eisen MB, Celniker SE. Computational identification of developmental enhancers: conservation and function of transcription factor binding-site clusters in Drosophila melanogaster and Drosophila pseudoobscura. Genome Biol 2004, 5:R61.
141. Lifanov AP, Makeev VJ, Nazina AG, Papatsenko DA. Homotypic regulatory clusters in Drosophila. Genome Res 2003, 13:579-588.
142. Arnone MI, Davidson EH. The hardwiring of development: organization and function of genomic regulatory systems. Development 1997, 124:1851-1864.
143. Hallikas O, Palin K, Sinjushina N, Rautiainen R, Partanen J, Ukkonen E, Taipale J. Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity. Cell 2006, 124:47-59.
144. Gotea V, Visel A, Westlund JM, Nobrega MA, Pennacchio LA, Ovcharenko I. Homotypic clusters of transcription factor binding sites are a key component of human promoters and enhancers. Genome Res 2010, 20:565-577.
145. He X, Duque TS, Sinha S. Evolutionary origins of transcription factor binding site clusters. Mol Biol Evol 2012, 29:1059-1070.
146. Hertel KJ, Lynch KW, Maniatis T. Common themes in the function of transcription and splicing enhancers. Curr Opin Cell Biol 1997, 9:350-357.
147. Lusk RW, Eisen MB. Evolutionary mirages: selection on binding site composition creates the illusion of conserved grammars in Drosophila enhancers. PLoS Genet 2010, 6:e1000829.
148. Papatsenko DA, Makeev VJ, Lifanov AP, Regnier M, Nazina AG, Desplan C. Extraction of functional binding sites from unique regulatory regions: the Drosophila early developmental enhancers. Genome Res 2002, 12:470-481.
149. Crocker J, Potter N, Erives A. Dynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers. Nat Commun 2010, 1:99.
150. Eddy SR. What is a hidden Markov model? Nat Biotechnol 2004, 22:1315-1316.
151. Frith MC, Li MC, Weng Z. Cluster-Buster: finding dense clusters of motifs in DNA sequences. Nucleic Acids Res 2003, 31:3666-3668.
152. Grad YH, Roth FP, Halfon MS, Church GM. Prediction of similarly acting cis-regulatory modules by subsequence profiling and comparative genomics in Drosophila melanogaster and D. pseudoobscura. Bioinformatics 2004, 20:2738-2750.
153. Sinha S, van Nimwegen E, Siggia ED. A probabilistic method to detect regulatory modules. Bioinformatics 2003, 19(suppl 1):i292-i301.
154. Crowley EM, Roeder K, Bina M. A statistical model for locating regulatory regions in genomic DNA. J Mol Biol 1997, 268:8-14.
155. Sinha S, Schroeder MD, Unnerstall U, Gaul U, Siggia ED. Cross-species comparison significantly improves genome-wide prediction of cis-regulatory modules in Drosophila. BMC Bioinformatics 2004, 5:129.
156. Blanchette M, Bataille AR, Chen X, Poitras C, Laganiere J, Lefebvre C, Deblois G, Giguere V, Ferretti V, Bergeron D, et al. Genome-wide computational prediction of transcriptional regulatory modules reveals new insights into human gene expression. Genome Res 2006, 16:656-668.
157. Sinha S, He X. MORPH: probabilistic alignment combined with hidden Markov models of cis-regulatory modules. PLoS Comput Biol 2007, 3:e216.
158. Warner JB, Philippakis AA, Jaeger SA, He FS, Lin J, Bulyk ML. Systematic identification of mammalian regulatory motifs' target genes and functions. Nat Methods 2008, 5:347-353.
159. Ivan A, Halfon MS, Sinha S. Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs. Genome Biol 2008, 9:R22.
160. Gordan R, Shen N, Dror I, Zhou T, Horton J, Rohs R, Bulyk ML. Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape. Cell Rep 2013, 3:1093-1104.
161. Siggers T, Duyzend MH, Reddy J, Khan S, Bulyk ML. Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex. Mol Syst Biol 2011, 7:555.
162. Zhou Q, Wong WH. CisModule: de novo discovery of cis-regulatory modules by hierarchical mixture modeling. Proc Natl Acad Sci USA 2004, 101:12114-12119.
163. Zhou Q, Wong WH. Coupling hidden Markov models for the discovery of cis-regulatory modules in multiple species. Ann Appl Stat 2007, 1:36-65.
164. Johnson DS, Zhou Q, Yagi K, Satoh N, Wong W, Sidow A. De novo discovery of a tissue-specific gene regulatory module in a chordate. Genome Res 2005, 15:1315-1324.
165. Rouault H, Santolini M, Schweisguth F, Hakim V. Imogene: identification of motifs and cis-regulatory modules underlying gene co-regulation. Nucleic Acids Res 2014, 42:6128-6145.
166. Kazemian M, Zhu Q, Halfon MS, Sinha S. Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison. Nucleic Acids Res 2011, 39:9463-9472.
167. Arunachalam M, Jayasurya K, Tomancak P, Ohler U. An alignment-free method to identify candidate orthologous enhancers in multiple Drosophila genomes. Bioinformatics 2010, 26:2109-2115.
168. Sosinsky A, Honig B, Mann RS, Califano A. Discovering transcriptional regulatory regions in Drosophila by a nonalignment method for phylogenetic footprinting. Proc Natl Acad Sci USA 2007, 104:6305-6310. doi:10.1073/pnas.0701614104.
169. Lee D, Karchin R, Beer MA. Discriminative prediction of mammalian enhancers from DNA sequence. Genome Res 2011, 21:2167-2180.
170. Fletez-Brant C, Lee D, McCallion AS, Beer MA. kmer-SVM: a web server for identifying predictive regulatory sequence features in genomic data sets. Nucleic Acids Res 2013, 41:W544-W556.
171. Schultheiss SJ, Busch W, Lohmann JU, Kohlbacher O, Ratsch G. KIRMES: kernel-based identification of regulatory modules in euchromatic sequences. Bioinformatics 2009, 25:2126-2133.
172. Taher L, Narlikar L, Ovcharenko I. CLARE: Cracking the LAnguage of Regulatory Elements. Bioinformatics 2012, 28:581-583.
173. Erwin GD, Oksenberg N, Truty RM, Kostka D, Murphy KK, Ahituv N, Pollard KS, Capra JA. Integrating diverse datasets improves developmental enhancer prediction. PLoS Comput Biol 2014, 10:e1003677.
174. Herrmann C, Van de Sande B, Potier D, Aerts S. i-cisTarget: an integrative genomics method for the prediction of regulatory features and cis-regulatory modules. Nucleic Acids Res 2012, 40:e114.
175. Aerts S, Quan XJ, Claeys A, Naval Sanchez M, Tate P, Yan J, Hassan BA. Robust target gene discovery through transcriptome perturbations and genome-wide enhancer predictions in Drosophila uncovers a regulatory basis for sensory specification. PLoS Biol 2010, 8:e1000435.
176. Kazemian M, Suryamohan K, Chen JY, Zhang Y, Samee MA, Halfon MS, Sinha S. Evidence for deep regulatory similarities in early developmental programs across highly diverged insects. Genome Biol Evol 2014, 6:2301-2320.
177. Wiegmann BM, Trautwein MD, Kim JW, Cassel BK, Bertone MA, Winterton SL, Yeates DK. Single-copy nuclear genes resolve the phylogeny of the holometabolous insects. BMC Biol 2009, 7:34.
178. Zdobnov EM, Bork P. Quantification of insect genome divergence. Trends Genet 2007, 23:16-20.
179. Kvon EZ, Kazmar T, Stampfel G, Yanez-Cuna JO, Pagani M, Schernhuber K, Dickson BJ, Stark A. Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature 2014, 512:91-95.
180. Noordermeer D, Duboule D. Chromatin looping and organization at developmentally regulated gene loci. WIREs Dev Biol 2013, 2:615-630.
181. Ghavi-Helm Y, Klein FA, Pakozdi T, Ciglar L, Noordermeer D, Huber W, Furlong EE. Enhancer loops appear stable during development and are associated with paused polymerase. Nature 2014, 512:96-100.
182. Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters. Nature 2012, 489:109-113.
183. Cook PR. A model for all genomes: the role of transcription factories. J Mol Biol 2010, 395:1-10.
184. Gallo SM, Gerrard DT, Miner D, Simich M, Des Soye B, Bergman CM, Halfon MS. REDfly v3.0: toward a comprehensive database of transcriptional regulatory elements in Drosophila. Nucleic Acids Res 2011, 39:D118-D123.
185. Costa M, Reeve S, Grumbling G, Osumi-Sutherland D. The Drosophila anatomy ontology. J Biomed Semantics 2013, 4:32.
186. St Pierre SE, Ponting L, Stefancsik R, McQuilton P. FlyBase 102-advanced approaches to interrogating FlyBase. Nucleic Acids Res 2014, 42:D780-D788.
187. Frankel N. Multiple layers of complexity in cis-regulatory regions of developmental genes. Dev Dyn 2012, 241:1857-1866.
188. Halfon MS. (Re)modeling the transcriptional enhancer. Nat Genet 2006, 38:1102-1103.
189. Juven-Gershon T, Kadonaga JT. Regulation of gene expression via the core promoter and the basal transcriptional machinery. Dev Biol 2010, 339:225-229.
190. Swanson CI, Evans NC, Barolo S. Structural rules and complex regulatory circuitry constrain expression of a Notch- and EGFR-regulated eye enhancer. Dev Cell 2010, 18:359-370.
191. Kwon D, Mucci D, Langlais KK, Americo JL, DeVido SK, Cheng Y, Kassis JA. Enhancer-promoter communication at the Drosophila engrailed locus. Development 2009, 136:3067-3075.
192. Atkinson TJ, Halfon MS. Regulation of gene expression in the genomic context. Comput Struct Biotechnol J 2014, 9:e201401001.
193. Harrison MM, Jenkins BV, O'Connor-Giles KM, Wildonger J. A CRISPR view of development. Genes Dev 2014, 28:1859-1872.