Enhancer variants: Evaluating functions in common disease

Genome Medicine

Volumn 6, Issue 10, 2014, Pages

  Corradin, Olivia ^a   Scacheri, Peter C ^a,b  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BREAST CANCER; CELLS BY BODY ANATOMY; CHROMATIN; COLORECTAL CANCER; CORONARY ARTERY DISEASE; CROHN DISEASE; DISEASE PREDISPOSITION; ENHANCER REGION; GENETIC ASSOCIATION; GENETIC RISK; GENETIC TRANSCRIPTION; HUMAN; MULTIPLE SCLEROSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PHENOTYPE; PRIORITY JOURNAL; PROSTATE CANCER; QUANTITATIVE TRAIT LOCUS; RESTLESS LEGS SYNDROME; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMIC LUPUS ERYTHEMATOSUS;

EID: 84928017429     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/s13073-014-0085-3     Document Type: Review

References (83)

1. Sasaki-Iwaoka H, Maruyama K, Endoh H, Komori T, Kato S, Kawashima H. A trans-acting enhancer modulates estrogen-mediated transcription of reporter genes in osteoblasts. J Bone Miner Res 1999, 14:248-255. 10.1359/jbmr.1999.14.2.248, 9933479.
2. Muller HP, Schaffner W. Transcriptional enhancer can act in trans. Trends Genet 1990, 6:300-304. 10.1016/0168-9525(90)90236-Y, 2238088.
3. Muller HP, Sogo JM, Schaffner W. An enhancer stimulates transcription in trans when attached to the promoter via a protein bridge. Cell 1989, 58:767-777. 10.1016/0092-8674(89)90110-4.
4. A Catalog of Published Genome-Wide Association Studies. []., http://www.genome.gov/gwasstudies
5. Gusev A, Hong Lee S, Neale BM, Trynka G, Vilhjalmsson BJ, Finucane H, Xu H, Zang C, Ripka S, Stahl E, Kahler AK, Hultman CM, Purcell SM, McCarroll SA, Daly M, Pasaniuc B, Sullivan PF, Wray NR, Raychaudhuri S, Price AL. Regulatory variants explain much more heritability than coding variants across 11 common diseases. bioRxiv 2014
6. Hazelett DJ, Rhie SK, Gaddis M, Yan C, Lakeland DL, Coetzee SG, Henderson BE, Noushmehr H, Cozen W, Kote-Jarai Z, Eeles RA, Easton DF, Haiman CA, Lu W, Farnham PJ, Coetzee GA. Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS Genet 2014, 10:e1004102. 10.1371/journal.pgen.1004102, 24497837.
7. Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L, Willis J, Cowper-Sal lari R, Lupien M, Markowitz S, Scacheri PC. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res 2014, 24:1-13. 10.1101/gr.164079.113, 24196873.
8. Rhie SK, Coetzee SG, Noushmehr H, Yan C, Kim JM, Haiman CA, Coetzee GA. Comprehensive functional annotation of seventy-one breast cancer risk loci. PLoS One 2013, 8:e63925. 10.1371/journal.pone.0063925, 23717510.
9. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, Wang W, Weng Z, Green RD, Crawford GE, Ren B. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 2007, 39:311-318. 10.1038/ng1966, 17277777.
10. Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, Ching KA, Antosiewicz-Bourget JE, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Crawford GE, Kellis M, Ren B. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 2009, 459:108-112. 10.1038/nature07829, 19295514.
11. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA, Frampton GM, Sharp PA, Boyer LA, Young RA, Jaenisch R. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 2010, 107:21931-21936. 10.1073/pnas.1016071107, 21106759.
12. 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. 10.1038/nature09692, 21160473.
13. Zentner GE, Tesar PJ, Scacheri PC. Epigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions. Genome Res 2011, 21:1273-1283. 10.1101/gr.122382.111, 21632746.
14. Taylor GC, Eskeland R, Hekimoglu-Balkan B, Pradeepa MM, Bickmore WA. H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction. Genome Res 2013, 23:2053-2065. 10.1101/gr.155028.113, 23990607.
15. Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME. Widespread transcription at neuronal activity-regulated enhancers. Nature 2010, 465:182-187. 10.1038/nature09033, 20393465.
16. Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, et al. An atlas of active enhancers across human cell types and tissues. Nature 2014, 507:455-461. 10.1038/nature12787, 24670763.
17. Birnbaum RY, Clowney EJ, Agamy O, Kim MJ, Zhao J, Yamanaka T, Pappalardo Z, Clarke SL, Wenger AM, Nguyen L, Gurrieri F, Everman DB, Schwartz CE, Birk OS, Bejerano G, Lomvardas S, Ahituv N. Coding exons function as tissue-specific enhancers of nearby genes. Genome Res 2012, 22:1059-1068. 10.1101/gr.133546.111, 22442009.
18. Stergachis AB, Haugen E, Shafer A, Wenqing F, Vernot B, Reynolds A, Raubitschek A, Ziegler S, LeProust EM, Akey JM, Stamatoyannopoulos JA. Exonic transcription factor binding directs codon choice and affects protein evolution. Science 2013, 342:1367-1372. 10.1126/science.1243490, 24337295.
19. Tumpel S, Cambronero F, Sims C, Krumlauf R, Wiedemann LM. A regulatory module embedded in the coding region of Hoxa2 controls expression in rhombomere 2. Proc Natl Acad Sci U S A 2008, 105:20077-20082. 10.1073/pnas.0806360105, 19104046.
20. Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E, Wang H, Reynolds AP, Sandstrom R, Qu H, Brody J, Shafer A, Neri F, Lee K, Kutyavin T, Stehling-Sun S, Johnson AK, Canfield TK, Giste E, Diegel M, Bates D, Hansen RS, Neph S, Sabo PJ, Heimfeld S, Raubitschek A, Ziegler S, Cotsapas C, Sotoodehnia N, Glass I, Sunyaev SR, et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 2012, 337:1190-1195. 10.1126/science.1222794, 22955828.
21. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X, Wang L, Issner R, Coyne M, Ku M, Durham T, Kellis M, Bernstein BE. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 2011, 473:43-49. 10.1038/nature09906, 21441907.
22. Trynka G, Sandor C, Han B, Xu H, Stranger BE, Liu XS, Raychaudhuri S. Chromatin marks identify critical cell types for fine mapping complex trait variants. Nat Genet 2013, 45:124-130. 10.1038/ng.2504, 23263488.
23. Pasquali L, Gaulton KJ, Rodriguez-Segui SA, Mularoni L, Miguel-Escalada I, Akerman I, Tena JJ, Morán I, Gómez-Marín C, van de Bunt M, Ponsa-Cobas J, Castro N, Nammo T, Cebola I, García-Hurtado J, Maestro MA, Pattou F, Piemonti L, Berney T, Gloyn AL, Ravassard P, G?mez-Skarmeta JL, Müller F, McCarthy MI, Ferrer J. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat Genet 2014, 46:136-143. 10.1038/ng.2870, 24413736.
24. Parker SC, Stitzel ML, Taylor DL, Orozco JM, Erdos MR, Akiyama JA, van Bueren KL, Chines PS, Narisu N, Black BL, Visel A, Pennacchio LA, Collins FS. Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants. Proc Natl Acad Sci U S A 2013, 110:17921-17926. 10.1073/pnas.1317023110, 24127591.
25. Stitzel ML, Sethupathy P, Pearson DS, Chines PS, Song L, Erdos MR, Welch R, Parker SC, Boyle AP, Scott LJ, Margulies EH, Boehnke M, Furey TS, Crawford GE, Collins FS. Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Cell Metab 2010, 12:443-455. 10.1016/j.cmet.2010.09.012, 21035756.
26. Akhtar-Zaidi B, Cowper-Sal-lari R, Corradin O, Saiakhova A, Bartels CF, Balasubramanian D, Myeroff L, Lutterbaugh J, Jarrar A, Kalady MF, Willis J, Moore JH, Tesar PJ, Laframboise T, Markowitz S, Lupien M, Scacheri PC. Epigenomic enhancer profiling defines a signature of colon cancer. Science 2012, 336:736-739. 10.1126/science.1217277, 22499810.
27. Alcina A, Fedetz M, Fernández Ó, Saiz A, Izquierdo G, Lucas M, Leyva L, García-León JA, Abad-Grau Mdel M, Alloza I, Antigüedad A, Garcia-Barcina MJ, Vandenbroeck K, Varadá J, de la Hera B, Arroyo R, Comabella M, Montalban X, Petit-Marty N, Navarro A, Otaegui D, Olascoaga J, Blanco Y, Urcelay E, Matesanz F. Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis. J Med Genet 2012, 50:25-33. 10.1136/jmedgenet-2012-101085, 23160276.
28. Bauer DE, Kamran SC, Lessard S, Xu J, Fujiwara Y, Lin C, Shao Z, Canver MC, Smith EC, Pinello L, Sabo PJ, Vierstra J, Voit RA, Yuan GC, Porteus MH, Stamatoyannopoulos JA, Lettre G, Orkin SH. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 2013, 342:253-257. 10.1126/science.1242088, 24115442.
29. Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nurnberg ST, Diaz R, Cheng K, Leeper NJ, Chen CH, Chang IS, Schadt EE, Hsiung CA, Assimes TL, Quertermous T. Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus. PLoS Genet 2013, 9:e1003652. 10.1371/journal.pgen.1003652, 23874238.
30. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gomez-Marin C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 2014, 507:371-375. 10.1038/nature13138, 24646999.
31. Harismendy O, Notani D, Song X, Rahim NG, Tanasa B, Heintzman N, Ren B, Fu XD, Topol EJ, Rosenfeld MG, Frazer KA. 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response. Nature 2011, 470:264-268. 10.1038/nature09753, 21307941.
32. Kapoor A, Sekar RB, Hansen NF, Fox-Talbot K, Morley M, Pihur V, Chatterjee S, Brandimarto J, Moravec CS, Pulit SL, Pfeufer A, Mullikin J, Ross M, Green ED, Bentley D, Newton-Cheh C, Boerwinkle E, Tomaselli GF, Cappola TP, Arking DE, Halushka MK, Chakravarti A. An enhancer polymorphism at the cardiomyocyte intercalated disc protein NOS1AP locus is a major regulator of the QT interval. Am J Hum Genet 2014, 94:854-869. 10.1016/j.ajhg.2014.05.001, 24857694.
33. Guenther CA, Tasic B, Luo L, Bedell MA, Kingsley DM. A molecular basis for classic blond hair color in Europeans. Nat Genet 2014, 46:748-752. 10.1038/ng.2991, 24880339.
34. Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M, Yao K, Kehoe SM, Lenz HJ, Haiman CA, Yan C, Henderson BE, Frenkel B, Barretina J, Bass A, Tabernero J, Baselga J, Regan MM, Manak JR, Shivdasani R, Coetzee GA, Freedman ML. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet 2009, 41:882-884. 10.1038/ng.403, 19561607.
35. Wasserman NF, Aneas I, Nobrega MA. An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer. Genome Res 2010, 20:1191-1197. 10.1101/gr.105361.110, 20627891.
36. Tuupanen S, Yan J, Turunen M, Gylfe AE, Kaasinen E, Li L, Eng C, Culver DA, Kalady MF, Pennison MJ, Pasche B, Manne U, de la Chapelle A, Hampel H, Henderson BE, Le Marchand L, Hautaniemi S, Askhtorab H, Smoot D, Sandler RS, Keku T, Kupfer SS, Ellis NA, Haiman CA, Taipale J, Aaltonen LA. Characterization of the colorectal cancer-associated enhancer MYC-335 at 8q24: the role of rs67491583. Cancer Genet 2012, 205:25-33. 10.1016/j.cancergen.2012.01.005, 22429595.
37. Spieler D, Kaffe M, Knauf F, Bessa J, Tena JJ, Giesert F, Schormair B, Tilch E, Lee H, Horsch M, Czamara D, Karbalai N, von Toerne C, Waldenberger M, Gieger C, Lichtner P, Claussnitzer M, Naumann R, Müller-Myhsok B, Torres M, Garrett L, Rozman J, Klingenspor M, Gailus-Durner V, Fuchs H, Hrabe de Angelis M, Beckers J, Hölter SM, Meitinger T, Hauck SM, et al. Restless legs syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalon. Genome Res 2014, 24:592-603. 10.1101/gr.166751.113, 24642863.
38. Cowper-Sal lari R, Zhang X, Wright JB, Bailey SD, Cole MD, Eeckhoute J, Moore JH, Lupien M. Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression. Nat Genet 2012, 44:1191-1198. 10.1038/ng.2416, 23001124.
39. Wright JB, Brown SJ, Cole MD. Upregulation of c-MYC in cis through a large chromatin loop linked to a cancer risk-associated single-nucleotide polymorphism in colorectal cancer cells. Mol Cell Biol 2010, 30:1411-1420. 10.1128/MCB.01384-09, 20065031.
40. Wang S, Wen F, Wiley GB, Kinter MT, Gaffney PM. An enhancer element harboring variants associated with systemic lupus erythematosus engages the TNFAIP3 promoter to influence A20 expression. PLoS Genet 2013, 9:e1003750. 10.1371/journal.pgen.1003750, 24039598.
41. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 2013, 153:307-319. 10.1016/j.cell.2013.03.035, 23582322.
42. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, Hoke HA, Young RA. Super-enhancers in the control of cell identity and disease. Cell 2013, 155:934-947. 10.1016/j.cell.2013.09.053, 24119843.
43. Zhang X, Cowper-Sal lari R, Bailey SD, Moore JH, Lupien M. Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus. Genome Res 2012, 22:1437-1446. 10.1101/gr.135665.111, 22665440.
44. Grice EA, Rochelle ES, Green ED, Chakravarti A, McCallion AS. Evaluation of the RET regulatory landscape reveals the biological relevance of a HSCR-implicated enhancer. Hum Mol Genet 2005, 14:3837-3845. 10.1093/hmg/ddi408, 16269442.
45. Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E, Lin S, Portnoy ME, Cutler DJ, Green EG, Chakravarti A. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 2005, 434:857-863. 10.1038/nature03467, 15829955.
46. Weedon MN, Cebola I, Patch AM, Flanagan SE, De Franco E, Caswell R, Rodríguez-Seguí SA, Shaw-Smith C, Cho CH, Lango Allen H, Houghton JA, Roth CL, Chen R, Hussain K, Marsh P, Vallier L, Murray A, Ellard S, Ferrer J, Hattersley AT. Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis. Nat Genet 2014, 46:61-64. 10.1038/ng.2826, 24212882.
47. Furniss D, Lettice LA, Taylor IB, Critchley PS, Giele H, Hill RE, Wilkie AO. A variant in the sonic hedgehog regulatory sequence (ZRS) is associated with triphalangeal thumb and deregulates expression in the developing limb. Hum Mol Genet 2008, 17:2417-2423. 10.1093/hmg/ddn141, 18463159.
48. Lettice LA. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Hum Mol Genet 2003, 12:1725-1735. 10.1093/hmg/ddg180, 12837695.
49. Kioussis D, Vanin E, deLange T, Flavell RA, Grosveld FG. β-Globin gene inactivation by DNA translocation in γβ-thalassaemia. Nature 1983, 306:662-666. 10.1038/306662a0, 6318113.
50. Semenza GL, Delgrosso K, Poncz M, Malladi P, Schwartz E, Surrey S. The silent carrier allele: β thalassemia without a mutation in the β-globin gene or its immediate flanking regions. Cell 1984, 39:123-128. 10.1016/0092-8674(84)90197-1, 6091904.
51. Boyle AP, Hong EL, Hariharan M, Cheng Y, Schaub MA, Kasowski M, Karczewski KJ, Park J, Hitz BC, Weng S, Cherry JM, Snyder M. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res 2012, 22:1790-1797. 10.1101/gr.137323.112, 22955989.
52. Ward LD, Kellis M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 2012, 40:D930-D934. 10.1093/nar/gkr917, 22064851.
53. Coetzee SG, Rhie SK, Berman BP, Coetzee GA, Noushmehr H. FunciSNP: an R/bioconductor tool integrating functional non-coding data sets with genetic association studies to identify candidate regulatory SNPs. Nucleic Acids Res 2012, 40:e139. 10.1093/nar/gks542, 22684628.
54. Khurana E, Fu Y, Colonna V, Mu XJ, Kang HM, Lappalainen T, Sboner A, Lochovsky L, Chen J, Harmanci A, Das J, Abyzov A, Balasubramanian S, Beal K, Chakravarty D, Challis D, Chen Y, Clarke D, Clarke L, Cunningham F, Evani US, Flicek P, Fragoza R, Garrison E, Gibbs R, G?m?s ZH, Herrero J, Kitabayashi N, Kong Y, Lage K, et al. Integrative annotation of variants from 1092 humans: application to cancer genomics. Science 2013, 342:1235587. 10.1126/science.1235587, 24092746.
55. Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters. Nature 2012, 489:109-113. 10.1038/nature11279, 22955621.
56. Jin F, Li Y, Dixon JR, Selvaraj S, Ye Z, Lee AY, Yen CA, Schmitt AD, Espinoza CA, Ren B. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 2013, 503:290-294. 24141950.
57. Li G, Ruan X, Auerbach RK, Sandhu KS, Zheng M, Wang P, Poh HM, Goh Y, Lim J, Zhang J, Sim HS, Peh SQ, Mulawadi FH, Ong CT, Orlov YL, Hong S, Zhang Z, Landt S, Raha D, Euskirchen G, Wei CL, Ge W, Wang H, Davis C, Fisher-Aylor KI, Mortazavi A, Gerstein M, Gingeras T, Wold B, Sun Y, et al. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 2012, 148:84-98. 10.1016/j.cell.2011.12.014, 22265404.
58. Zhang Y, Wong CH, Birnbaum RY, Li G, Favaro R, Ngan CY, Lim J, Tai E, Poh HM, Wong E, Mulawadi FH, Sung WK, Nicolis S, Ahituv N, Ruan Y, Wei CL. Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations. Nature 2013, 504:306-310. 10.1038/nature12716, 24213634.
59. Bickmore WA. The spatial organization of the human genome. Ann Rev Genomics Hum Genet 2013, 14:67-84. 10.1146/annurev-genom-091212-153515.
60. Williamson I, Eskeland R, Lettice LA, Hill AE, Boyle S, Grimes GR, Hill RE, Bickmore WA. Anterior-posterior differences in HoxD chromatin topology in limb development. Development 2012, 139:3157-3167. 10.1242/dev.081174, 22872084.
61. Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science 2002, 295:1306-1311. 10.1126/science.1067799, 11847345.
62. Simonis M, Klous P, Splinter E, Moshkin Y, Willemsen R, de Wit E, van Steensel B, de Laat W. Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat Genet 2006, 38:1348-1354. 10.1038/ng1896, 17033623.
63. 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, 22215806.
64. Sajan SA, Hawkins RD. Methods for identifying higher-order chromatin structure. Ann Rev Genomics Hum Genet 2012, 13:59-82. 10.1146/annurev-genom-090711-163818.
65. Panne D. The enhanceosome. Curr Opin Struct Biol 2008, 18:236-242. 10.1016/j.sbi.2007.12.002, 18206362.
66. Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, Garg K, John S, Sandstrom R, Bates D, Boatman L, Canfield TK, Diegel M, Dunn D, Ebersol AK, Frum T, Giste E, Johnson AK, Johnson EM, Kutyavin T, Lajoie B, Lee BK, Lee K, London D, Lotakis D, Neph S, et al. The accessible chromatin landscape of the human genome. Nature 2012, 489:75-82. 10.1038/nature11232, 22955617.
67. Shen Y, Yue F, McCleary DF, Ye Z, Edsall L, Kuan S, Wagner U, Dixon J, Lee L, Lobanenkov VV, Ren B. A map of the cis-regulatory sequences in the mouse genome. Nature 2012, 488:116-120. 10.1038/nature11243, 22763441.
68. Factor DC, Corradin O, Zentner GE, Saiakhova A, Song L, Chenoweth JG, McKay RD, Crawford GE, Scacheri PC, Tesar PJ. Epigenomic comparison reveals activation of seed enhancers during transition from naive to primed pluripotency. Cell Stem Cell 2014, 14:854-863. 10.1016/j.stem.2014.05.005, 24905169.
69. He B, Chen C, Teng L, Tan K. Global view of enhancer-promoter interactome in human cells. Proc Natl Acad Sci U S A 2014, 111:E2191-E2199. 10.1073/pnas.1320308111, 24821768.
70. Sheffield NC, Thurman RE, Song L, Safi A, Stamatoyannopoulos JA, Lenhard B, Crawford GE, Furey TS. Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions. Genome Res 2013, 23:777-788. http://dnase.genome.duke.edu/, 10.1101/gr.152140.112, 23482648.
71. Fairfax BP, Makino S, Radhakrishnan J, Plant K, Leslie S, Dilthey A, Ellis P, Langford C, Vannberg FO, Knight JC. Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles. Nat Genet 2012, 44:502-510. 10.1038/ng.2205, 22446964.
72. Raj T, Rothamel K, Mostafavi S, Ye C, Lee MN, Replogle JM, Feng T, Lee M, Asinovski N, Frohlich I, Imboywa S, Von Korff A, Okada Y, Patsopoulos NA, Davis S, McCabe C, Paik HI, Srivastava GP, Raychaudhuri S, Hafler DA, Koller D, Regev A, Hacohen N, Mathis D, Benoist C, Stranger BE, De Jager PL. Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science 2014, 344:519-523. 10.1126/science.1249547, 24786080.
73. Patwardhan RP, Hiatt JB, Witten DM, Kim MJ, Smith RP, May D, Lee C, Andrie JM, Lee SI, Cooper GM, Ahituv N, Pennacchio LA, Shendure J. Massively parallel functional dissection of mammalian enhancers in vivo. Nat Biotechnol 2012, 30:265-270. 10.1038/nbt.2136, 22371081.
74. Kheradpour P, Ernst J, Melnikov A, Rogov P, Wang L, Zhang X, Alston J, Mikkelsen TS, Kellis M. Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay. Genome Res 2013, 23:800-811. 10.1101/gr.144899.112, 23512712.
75. Shlyueva D, Stampfel G, Stark A. Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet 2014, 15:272-286. 10.1038/nrg3682, 24614317.
76. Gaulton KJ, Nammo T, Pasquali L, Simon JM, Giresi PG, Fogarty MP, Panhuis TM, Mieczkowski P, Secchi A, Bosco D, Berney T, Montanya E, Mohlke KL, Lieb JD, Ferrer J. A map of open chromatin in human pancreatic islets. Nat Genet 2010, 42:255-259. 10.1038/ng.530, 20118932.
77. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007, 447:799-816. 10.1038/nature05874.
78. A second generation human haplotype map of over 3.1 million SNPs. Nature 2007, 449:851-861. 10.1038/nature06258.
79. Integrating common and rare genetic variation in diverse human populations. Nature 2010, 467:52-58. 10.1038/nature09298.
80. Ongen H, Andersen CL, Bramsen JB, Oster B, Rasmussen MH, Ferreira PG, Sandoval J, Vidal E, Whiffin N, Planchon A, Padioleau I, Bielser D, Romano L, Tomlinson I, Houlston RS, Esteller M, Orntoft TF, Dermitzakis ET. Putative cis-regulatory drivers in colorectal cancer. Nature 2014, 512:87-90. 25079323.
81. Fairfax BP, Humburg P, Makino S, Naranbhai V, Wong D, Lau E, Jostins L, Plant K, Andrews R, McGee C, Knight JC. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science 2014, 343:1246949. 10.1126/science.1246949, 24604202.
82. Claussnitzer M, Dankel SN, Klocke B, Grallert H, Glunk V, Berulava T, Lee H, Oskolkov N, Fadista J, Ehlers K, Wahl S, Hoffmann C, Qian K, R?nn T, Riess H, Müller-Nurasyid M, Bretschneider N, Schroeder T, Skurk T, Horsthemke B, Spieler D, Klingenspor M, Seifert M, Kern MJ, Mejhert N, Dahlman I, Hansson O, Hauck SM, et al. Leveraging cross-species transcription factor binding site patterns: from diabetes risk loci to disease mechanisms. Cell 2014, 156:343-358. 10.1016/j.cell.2013.10.058, 24439387.
83. Kilpinen H, Waszak SM, Gschwind AR, Raghav SK, Witwicki RM, Orioli A, Migliavacca E, Wiederkehr M, Gutierrez-Arcelus M, Panousis NI, Yurovsky A, Lappalainen T, Romano-Palumbo L, Planchon A, Bielser D, Bryois J, Padioleau I, Udin G, Thurnheer S, Hacker D, Core LJ, Lis JT, Hernandez N, Reymond A, Deplancke B, Dermitzakis ET. Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription. Science 2013, 342:744-747. 10.1126/science.1242463, 24136355.