Pick, L, Heffer, A. Hox gene evolution: multiple mechanisms contributing to evolutionary novelties. Ann N Y Acad Sci 2012, 1256:15–32.
Smith, E, Shilatifard, A. Enhancer biology and enhanceropathies. Nat Struct Mol Biol 2014, 21:210–219.
Bulger, M, Groudine, M. Functional and mechanistic diversity of distal transcription enhancers. Cell 2011, 144:327–339.
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.
Ong, CT, Corces, VG. Enhancers: emerging roles in cell fate specification. EMBO Rep 2012, 13:423–430.
Spitz, F, Furlong, EE. Transcription factors: from enhancer binding to developmental control. Nat Rev Genet 2012, 13:613–626.
Schaffner, W. Enhancer. In: Encyclopedia of Molecular Biology. John Wiley %26 Sons; 2002. doi:10.1002/047120918X.emb0478.
Maston, GA, Evans, SK, Green, MR. Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet 2006, 7:29–59.
Weake, VM, Workman, JL. Inducible gene expression: diverse regulatory mechanisms. Nat Rev Genet 2010, 11:426–437.
Calo, E, Wysocka, J. Modification of enhancer chromatin: what, how, and why? Mol Cell 2013, 49:825–837.
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.
Lam, MT, Li, W, Rosenfeld, MG, Glass, CK. Enhancer RNAs and regulated transcriptional programs. Trends Biochem Sci 2014, 39:170–182.
Mousavi, K, Zare, H, Koulnis, M, Sartorelli, V. The emerging roles of eRNAs in transcriptional regulatory networks. RNA Biol 2014, 11:106–110.
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.
Bajic, VB, Tan, SL, Suzuki, Y, Sugano, S. Promoter prediction analysis on the whole human genome. Nat Biotechnol 2004, 22:1467–1473.
Wang, Z, Chen, Y, Li, Y. A brief review of computational gene prediction methods. Genomics Proteomics Bioinformatics 2004, 2:216–221.
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.
D`Haeseleer, P. What are DNA sequence motifs? Nat Biotechnol 2006, 24:423–425.
Schneider, TD, Stephens, RM. Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 1990, 18:6097–6100.
Hertz, GZ, Stormo, GD. Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics 1999, 15:563–577.
Stormo, GD. DNA binding sites: representation and discovery. Bioinformatics 2000, 16:16–23.
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.
Stormo, GD. Modeling the specificity of protein‐DNA interactions. Cold Spring Harb Symp Quant Biol 2013, 1:115–130.
GuhaThakurta, D. Computational identification of transcriptional regulatory elements in DNA sequence. Nucleic Acids Res 2006, 34:3585–3598. doi:10.1093/nar/gkl372.
Pavesi, G, Mauri, G, Pesole, G. In silico representation and discovery of transcription factor binding sites. Brief Bioinform 2004, 5:217–236.
Jolma, A, Taipale, J. Methods for analysis of transcription factor DNA‐binding specificity in vitro. Subcell Biochem 2011, 52:155–173.
MacIsaac, KD, Fraenkel, E. Practical strategies for discovering regulatory DNA sequence motifs. PLoS Comput Biol 2006, 2:e36.
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.
Swanson, CI, Schwimmer, DB, Barolo, S. Rapid evolutionary rewiring of a structurally constrained eye enhancer. Curr Biol 2011, 21:1186–1196.
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.
Tanay, A. Extensive low‐affinity transcriptional interactions in the yeast genome. Genome Res 2006, 16:962–972.
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.
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.
Maerkl, SJ, Quake, SR. A systems approach to measuring the binding energy landscapes of transcription factors. Science 2007, 315:233–237.
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.
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.
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.
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.
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.
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.
Buck, MJ, Lieb, JD. ChIP‐chip: considerations for the design, analysis, and application of genome‐wide chromatin immunoprecipitation experiments. Genomics 2004, 83:349–360.
Mardis, ER. ChIP‐seq: welcome to the new frontier. Nat Methods 2007, 4:613–614.
van Steensel, B, Henikoff, S. Identification of in vivo DNA targets of chromatin proteins using tethered dam methyltransferase. Nat Biotechnol 2000, 18:424–428.
Rhee, HS, Pugh, BF. Comprehensive genome‐wide protein‐DNA interactions detected at single‐nucleotide resolution. Cell 2011, 147:1408–1419.
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.
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.
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.
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.
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.
Wasserman, WW, Sandelin, A. Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet 2004, 5:276–287.
Banerji, J, Rusconi, S, Schaffner, W. Expression of a β‐globin gene is enhanced by remote SV40 DNA sequences. Cell 1981, 27:299–308.
Shlyueva, D, Stampfel, G, Stark, A. Transcriptional enhancers: from properties to genome‐wide predictions. Nat Rev Genet 2014, 15:272–286.
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.
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.
Davidson, EH. The Regulatory Genome : Gene Regulatory Networks in Development and Evolution. Burlington, MA/San Diego, CA: Academic Press; 2006.
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.
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.
Mann, RS, Carroll, SB. Molecular mechanisms of selector gene function and evolution. Curr Opin Genet Dev 2002, 12:592–600.
Britten, RJ, Davidson, EH. Gene regulation for higher cells: a theory. Science 1969, 165:349–357.
Ford, E, Thanos, D. The transcriptional code of human IFN‐β gene expression. Biochim Biophys Acta 2010, 1799:328–336.
Arnosti, DN, Kulkarni, MM. Transcriptional enhancers: intelligent enhanceosomes or flexible billboards? J Cell Biochem 2005, 94:890–898.
Liu, F, Posakony, JW. Role of architecture in the function and specificity of two Notch‐regulated transcriptional enhancer modules. PLoS Genet 2012, 8:e1002796.
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.
Zinzen, RP, Girardot, C, Gagneur, J, Braun, M, Furlong, EE. Combinatorial binding predicts spatio‐temporal cis‐regulatory activity. Nature 2009, 462:65–70.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Park, D, Lee, Y, Bhupindersingh, G, Iyer, VR. Widespread misinterpretable ChIP‐seq bias in yeast. PLoS One 2013, 8:e83506.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ernst, J, Kellis, M. ChromHMM: automating chromatin‐state discovery and characterization. Nat Methods 2012, 9:215–216.
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.
Kwasnieski, JC, Fiore, C, Chaudhari, HG, Cohen, BA. High‐throughput functional testing of ENCODE segmentation predictions. Genome Res 2014, 24:1595–1602.
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.
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.
Bell, O, Tiwari, VK, Thoma, NH, Schubeler, D. Determinants and dynamics of genome accessibility. Nat Rev Genet 2011, 12:554–564.
Zaret, KS, Carroll, JS. Pioneer transcription factors: establishing competence for gene expression. Genes Dev 2011, 25:2227–2241.
Gross, DS, Garrard, WT. Nuclease hypersensitive sites in chromatin. Annu Rev Biochem 1988, 57:159–197.
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.
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.
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.
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.
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.
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.
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.
Nam, J, Davidson, EH. Barcoded DNA‐tag reporters for multiplex cis‐regulatory analysis. PLoS One 2012, 7:e35934.
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.
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.
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.
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.
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.
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.
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.
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.
Aerts, S. Computational strategies for the genome‐wide identification of cis‐regulatory elements and transcriptional targets. Curr Top Dev Biol 2012, 98:121–145.
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.
Van Loo, P, Marynen, P. Computational methods for the detection of cis‐regulatory modules. Brief Bioinform 2009, 10:509–524.
Miller, W, Makova, KD, Nekrutenko, A, Hardison, RC. Comparative genomics. Annu Rev Genomics Hum Genet 2004, 5:15–56.
Hardison, RC. Conserved noncoding sequences are reliable guides to regulatory elements. Trends Genet 2000, 16:369–372.
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.
Su, J, Teichmann, SA, Down, TA. Assessing computational methods of cis‐regulatory module prediction. PLoS Comput Biol 2010, 6:e1001020.
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.
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.
Nobrega, MA, Ovcharenko, I, Afzal, V, Rubin, EM. Scanning human gene deserts for long‐range enhancers. Science 2003, 302:413.
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.
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.
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.
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.
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.
Hardison, RC, Taylor, J. Genomic approaches towards finding cis‐regulatory modules in animals. Nat Rev Genet 2012, 13:469–483.
Rubinstein, M, de Souza, FS. Evolution of transcriptional enhancers and animal diversity. Philos Trans R Soc Lond B Biol Sci 2013, 368:20130017.
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.
Ludwig, MZ, Bergman, C, Patel, NH, Kreitman, M. Evidence for stabilizing selection in a eukaryotic enhancer element. Nature 2000, 403:564–567.
Vinga, S, Almeida, J. Alignment‐free sequence comparison—a review. Bioinformatics 2003, 19:513–523.
Wasserman, WW, Fickett, JW. Identification of regulatory regions which confer muscle‐specific gene expression. J Mol Biol 1998, 278:167–181.
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.
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.
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.
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.
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.
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.
Lifanov, AP, Makeev, VJ, Nazina, AG, Papatsenko, DA. Homotypic regulatory clusters in Drosophila. Genome Res 2003, 13:579–588.
Arnone, MI, Davidson, EH. The hardwiring of development: organization and function of genomic regulatory systems. Development 1997, 124:1851–1864.
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.
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.
He, X, Duque, TS, Sinha, S. Evolutionary origins of transcription factor binding site clusters. Mol Biol Evol 2012, 29:1059–1070.
Hertel, KJ, Lynch, KW, Maniatis, T. Common themes in the function of transcription and splicing enhancers. Curr Opin Cell Biol 1997, 9:350–357.
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.
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.
Crocker, J, Potter, N, Erives, A. Dynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers. Nat Commun 2010, 1:99.
Eddy, SR. What is a hidden Markov model? Nat Biotechnol 2004, 22:1315–1316.
Frith, MC, Li, MC, Weng, Z. Cluster‐Buster: finding dense clusters of motifs in DNA sequences. Nucleic Acids Res 2003, 31:3666–3668.
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.
Sinha, S, van Nimwegen, E, Siggia, ED. A probabilistic method to detect regulatory modules. Bioinformatics 2003, 19(suppl 1):i292–i301.
Crowley, EM, Roeder, K, Bina, M. A statistical model for locating regulatory regions in genomic DNA. J Mol Biol 1997, 268:8–14.
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.
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.
Sinha, S, He, X. MORPH: probabilistic alignment combined with hidden Markov models of cis‐regulatory modules. PLoS Comput Biol 2007, 3:e216.
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.
Ivan, A, Halfon, MS, Sinha, S. Computational discovery of cis‐regulatory modules in Drosophila without prior knowledge of motifs. Genome Biol 2008, 9:R22.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lee, D, Karchin, R, Beer, MA. Discriminative prediction of mammalian enhancers from DNA sequence. Genome Res 2011, 21:2167–2180.
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.
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.
Taher, L, Narlikar, L, Ovcharenko, I. CLARE: Cracking the LAnguage of Regulatory Elements. Bioinformatics 2012, 28:581–583.
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.
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.
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.
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.
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.
Zdobnov, EM, Bork, P. Quantification of insect genome divergence. Trends Genet 2007, 23:16–20.
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.
Noordermeer, D, Duboule, D. Chromatin looping and organization at developmentally regulated gene loci. WIREs Dev Biol 2013, 2:615–630.
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.
Sanyal, A, Lajoie, BR, Jain, G, Dekker, J. The long‐range interaction landscape of gene promoters. Nature 2012, 489:109–113.
Cook, PR. A model for all genomes: the role of transcription factories. J Mol Biol 2010, 395:1–10.
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.
Costa, M, Reeve, S, Grumbling, G, Osumi‐Sutherland, D. The Drosophila anatomy ontology. J Biomed Semantics 2013, 4:32.
St Pierre, SE, Ponting, L, Stefancsik, R, McQuilton, P. FlyBase 102—advanced approaches to interrogating FlyBase. Nucleic Acids Res 2014, 42:D780–D788.
Frankel, N. Multiple layers of complexity in cis‐regulatory regions of developmental genes. Dev Dyn 2012, 241:1857–1866.
Halfon, MS. (Re)modeling the transcriptional enhancer. Nat Genet 2006, 38:1102–1103.
Juven‐Gershon, T, Kadonaga, JT. Regulation of gene expression via the core promoter and the basal transcriptional machinery. Dev Biol 2010, 339:225–229.
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.
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.
Atkinson, TJ, Halfon, MS. Regulation of gene expression in the genomic context. Comput Struct Biotechnol J 2014, 9:e201401001.
Harrison, MM, Jenkins, BV, O`Connor‐Giles, KM, Wildonger, J. A CRISPR view of development. Genes Dev 2014, 28:1859–1872.