Gene Regulatory Elements, Major Drivers of Human Disease

Literature Cited

1. Akhtar-Zaidi B, Cowper-Sal·lari R, Corradin O, Saiakhova A, Bartels CF. 1.  et al. 2012. Epigenomic enhancer profiling defines a signature of colon cancer. Science 336:736–39 [Google Scholar]
2. Alon U. 2.  2007. An Introduction to Systems Biology: Design Principles of Biological Circuits Boca Raton, FL: Chapman & Hall/CRC
3. Alves MM, Sribudiani Y, Brouwer RW, Amiel J, Antinolo G. 3.  et al. 2013. Contribution of rare and common variants determine complex diseases—Hirschsprung disease as a model. Dev. Biol. 382:320–29 [Google Scholar]
4. Anderson E, Peluso S, Lettice LA, Hill RE. 4.  2012. Human limb abnormalities caused by disruption of hedgehog signaling. Trends Genet 28:364–73 [Google Scholar]
5. Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J. 5.  et al. 2014. An atlas of active enhancers across human cell types and tissues. Nature 507:455–61 [Google Scholar]
6. Arnold CD, Gerlach D, Stelzer C, Boryn LM, Rath M, Stark A. 6.  2013. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339:1074–77 [Google Scholar]
7. Aytes A, Mitrofanova A, Lefebvre C, Alvarez MJ, Castillo-Martin M. 7.  et al. 2014. Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell 25:638–51 [Google Scholar]
8. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE. 8.  et al. 2007. High-resolution profiling of histone methylations in the human genome. Cell 129:823–37 [Google Scholar]
9. Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK. 9.  et al. 2005. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120:169–81 [Google Scholar]
10. Bernstein BE, Stamatoyannopoulos JA, Costello JF, Ren B, Milosavljevic A. 10.  et al. 2010. The NIH Roadmap Epigenomics Mapping Consortium. Nat. Biotechnol. 28:1045–48 [Google Scholar]
11. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. 11.  2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10:1213–18 [Google Scholar]
12. Canver MC, Smith EC, Sher F, Pinello L, Sanjana NE. 12.  et al. 2015. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature 527:192–97 [Google Scholar]
13. Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X. 13.  et al. 2010. The transcriptional network for mesenchymal transformation of brain tumours. Nature 463:318–25 [Google Scholar]
14. Chakravarti A, McCallion AS, Lyonnet S. 14.  2001. Hirschsprung disease. The Online Metabolic and Molecular Bases of Inherited Disease D Valle, AL Beaudet, B Vogelstein, KW Kinzler, SE Antonarakis et al. chap. 251 New York: McGraw-Hill https://doi.org/10.1036/ommbid.291 [Crossref] [Google Scholar]
15. Chatterjee S, Kapoor A, Akiyama JA, Auer DR, Lee D. 15.  et al. 2016. Enhancer variants synergistically drive dysfunction of a gene regulatory network in Hirschsprung disease. Cell 167:355–68 [Google Scholar]
16. Chavez A, Scheiman J, Vora S, Pruitt BW, Tuttle M. 16.  et al. 2015. Highly efficient Cas9-mediated transcriptional programming. Nat. Methods 12:326–28 [Google Scholar]
17. Chen JC, Alvarez MJ, Talos F, Dhruv H, Rieckhof GE. 17.  et al. 2014. Identification of causal genetic drivers of human disease through systems-level analysis of regulatory networks. Cell 159:402–14 [Google Scholar]
18. Church C, Moir L, McMurray F, Girard C, Banks GT. 18.  et al. 2010. Overexpression of Fto leads to increased food intake and results in obesity. Nat. Genet. 42:1086–92 [Google Scholar]
19. Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W. 19.  et al. 2015. FTO obesity variant circuitry and adipocyte browning in humans. N. Engl. J. Med. 373:895–907 [Google Scholar]
20. Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L, Willis J. 20.  et al. 2014. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res 24:1–13 [Google Scholar]
21. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW. 21.  et al. 2010. Histone H3K27ac separates active from poised enhancers and predicts developmental state. PNAS 107:21931–36 [Google Scholar]
22. Datlinger P, Rendeiro AF, Schmidl C, Krausgruber C, Traxler P. 22.  et al. 2017. Pooled CRISPR screening with single-cell transcriptome readout. Nat. Methods 14:297–301 [Google Scholar]
23. Davidson EH. 23.  2006. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution Burlington, MA: Academic
24. Deans RM, Morgens DW, Okesli A, Pillay S, Horlbeck MA. 24.  et al. 2016. Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification. Nat. Chem. Biol. 12:361–66 [Google Scholar]
25. di Iulio J, Bartha I, Wong E, Yu H-C, Hicks M. 25.  et al. 2016. The human functional genome defined by genetic diversity. bioRxiv 082362. https://doi.org/10.1101/082362 [Crossref]
26. Diao Y, Li B, Meng Z, Jung I, Lee AY. 26.  et al. 2016. A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening. Genome Res 26:397–405 [Google Scholar]
27. Dickel DE, Barozzi I, Zhu Y, Fukuda-Yuzawa Y, Osterwalder M. 27.  et al. 2016. Genome-wide compendium and functional assessment of in vivo heart enhancers. Nat. Commun. 7:12923 [Google Scholar]
28. Dickel DE, Zhu Y, Nord AS, Wylie JN, Akiyama JA. 28.  et al. 2014. Function-based identification of mammalian enhancers using site-specific integration. Nat. Methods 11:566–71 [Google Scholar]
29. Dina C, Meyre D, Gallina S, Durand E, Körner A. 29.  et al. 2007. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat. Genet. 39:724–26 [Google Scholar]
30. Dixon JR, Jung I, Selvaraj S, Shen Y, Antosiewicz-Bourget JE. 30.  et al. 2015. Chromatin architecture reorganization during stem cell differentiation. Nature 518:331–36 [Google Scholar]
31. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y. 31.  et al. 2012. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–80 [Google Scholar]
32. Driscoll MC, Dobkin CS, Alter BP. 32.  1989. γδβ-Thalassemia due to a de novo mutation deleting the 5′ β-globin gene activation-region hypersensitive sites. PNAS 86:7470–74 [Google Scholar]
33. Emilsson V, Thorleifsson G, Zhang B, Leonardson AS, Zink F. 33.  et al. 2008. Genetics of gene expression and its effect on disease. Nature 452:423–28 [Google Scholar]
34. Emison ES, Garcia-Barcelo M, Grice EA, Lantieri F, Amiel J. 34.  et al. 2010. Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. Am. J. Hum. Genet. 87:60–74 [Google Scholar]
35. Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E. 35.  et al. 2005. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 434:857–63 [Google Scholar]
36. 36. ENCODE Proj. Consort. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816 [Google Scholar]
37. Epstein DJ, McMahon AP, Joyner AL. 37.  1999. Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and -independent mechanisms. Development 126:281–92 [Google Scholar]
38. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD. 38.  et al. 2011. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473:43–49 [Google Scholar]
39. Fairfax BP, Makino S, Radhakrishnan J, Plant K, Leslie S. 39.  et al. 2012. Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles. Nat. Genet. 44:502–10 [Google Scholar]
40. Fang R, Yu M, Li G, Chee S, Liu T. 40.  et al. 2016. Mapping of long-range chromatin interactions by proximity ligation-assisted ChIP-seq. Cell Res 26:1345–48 [Google Scholar]
41. 41. FANTOM Consort., RIKEN PMI CLST (DGT). 2014. A promoter-level mammalian expression atlas. Nature 507:462–70 [Google Scholar]
42. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T. 42.  et al. 2009. Inactivation of the Fto gene protects from obesity. Nature 458:894–98 [Google Scholar]
43. Franke M, Ibrahim DM, Andrey G, Schwarzer W, Heinrich V. 43.  et al. 2016. Formation of new chromatin domains determines pathogenicity of genomic duplications. Nature 538:265–69 [Google Scholar]
44. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM. 44.  et al. 2007. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–94 [Google Scholar]
45. Fulco CP, Munschauer M, Anyoha R, Munson G, Grossman SR. 45.  et al. 2016. Systematic mapping of functional enhancer-promoter connections with CRISPR interference. Science 354:769–73 [Google Scholar]
46. Fullwood MJ, Liu MH, Pan YF, Liu J, Xu H. 46.  et al. 2009. An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 462:58–64 [Google Scholar]
47. Gavrilov A, Eivazova E, Priozhkova I, Lipinski M, Razin S, Vassetzky Y. 47.  2009. Chromosome conformation capture (from 3C to 5C) and its ChIP-based modification. Methods Mol. Biol. 567:171–88 [Google Scholar]
48. Gilad Y, Rifkin SA, Pritchard JK. 48.  2008. Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet 24:408–15 [Google Scholar]
49. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y. 49.  et al. 2014. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159:647–61 [Google Scholar]
50. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA. 50.  et al. 2013. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:442–51 [Google Scholar]
51. Greenawalt DM, Dobrin R, Chudin E, Hatoum IJ, Suver C. 51.  et al. 2011. A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort. Genome Res 21:1008–16 [Google Scholar]
52. 52. GTEx Consort. 2013. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45:580–85 [Google Scholar]
53. Guo Y, Xu Q, Canzio D, Shou J, Li J. 53.  et al. 2015. CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell 162:900–10 [Google Scholar]
54. Gustafsson M, Gawel DR, Alfredsson L, Baranzini S, Bjorkander J. 54.  et al. 2015. A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases. Sci. Transl. Med. 7:313ra178 [Google Scholar]
55. Harismendy O, Notani D, Song X, Rahim NG, Tanasa B. 55.  et al. 2011. 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response. Nature 470:264–68 [Google Scholar]
56. Harris MB, Mostecki J, Rothman PB. 56.  2005. Repression of an interleukin-4-responsive promoter requires cooperative BCL-6 function. J. Biol. Chem. 280:13114–21 [Google Scholar]
57. Hazelett DJ, Rhie SK, Gaddis M, Yan C, Lakeland DL. 57.  et al. 2014. Comprehensive functional annotation of 77 prostate cancer risk loci. PLOS Genet 10:e1004102 [Google Scholar]
58. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW. 58.  et al. 2007. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39:311–18 [Google Scholar]
59. Hilton IB, D'Ippolito AM, Vockley CM, Thakore PI, Crawford GE. 59.  et al. 2015. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat. Biotechnol. 33:510–17 [Google Scholar]
60. Horlbeck MA, Gilbert LA, Villalta JE, Adamson B, Pak RA. 60.  et al. 2016. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. eLife 5:e19760 [Google Scholar]
61. Hu X, Kim H, Stahl E, Plenge R, Daly M, Raychaudhuri S. 61.  2011. Integrating autoimmune risk loci with gene-expression data identifies specific pathogenic immune cell subsets. Am. J. Hum. Genet. 89:496–506 [Google Scholar]
62. Inoue F, Ahituv N. 62.  2015. Decoding enhancers using massively parallel reporter assays. Genomics 106:159–64 [Google Scholar]
63. Inoue F, Kircher M, Martin B, Cooper GM, Witten DM. 63.  et al. 2017. A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity. Genome Res 27:38–52 [Google Scholar]
64. Kapoor A, Jiang Q, Chatterjee S, Chakraborty P, Sosa MX. 64.  et al. 2015. Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms. Hum. Mol. Genet 24:2997–3003 [Google Scholar]
65. Kapoor A, Sekar RB, Hansen NF, Fox-Talbot K, Morley M. 65.  et al. 2014. An enhancer polymorphism at the cardiomyocyte intercalated disc protein NOS1AP locus is a major regulator of the QT interval. Am. J. Hum. Genet. 94:854–69 [Google Scholar]
66. Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A. 66.  et al. 2014. Defining functional DNA elements in the human genome. PNAS 111:6131–38 [Google Scholar]
67. Kheradpour P, Ernst J, Melnikov A, Rogov P, Wang L. 67.  et al. 2013. Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay. Genome Res 23:800–11 [Google Scholar]
68. Kilpelainen TO, Qi L, Brage S, Sharp SJ, Sonestedt E. 68.  et al. 2011. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLOS Med 8:e1001116 [Google Scholar]
69. Kinney JB, Murugan A, Callan CG Jr., Cox EC. 69.  2010. Using deep sequencing to characterize the biophysical mechanism of a transcriptional regulatory sequence. PNAS 107:9158–63 [Google Scholar]
70. Kioussis D, Vanin E, deLange T, Flavell RA, Grosveld FG. 70.  1983. Beta-globin gene inactivation by DNA translocation in gamma beta-thalassaemia. Nature 306:662–66 [Google Scholar]
71. Kleinjan DJ, van Heyningen V. 71.  1998. Position effect in human genetic disease. Hum. Mol. Genet. 7:1611–18 [Google Scholar]
72. Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO. 72.  et al. 2015. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517:583–88 [Google Scholar]
73. Korkmaz G, Lopes R, Ugalde AP, Nevedomskaya E, Han R. 73.  et al. 2016. Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Nat. Biotechnol. 34:192–98 [Google Scholar]
74. Kwasnieski JC, Fiore C, Chaudhari HG, Cohen BA. 74.  2014. High-throughput functional testing of ENCODE segmentation predictions. Genome Res 24:1595–602 [Google Scholar]
75. Lanzuolo C, Roure V, Dekker J, Bantignies F, Orlando V. 75.  2007. Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex. Nat. Cell Biol. 9:1167–74 [Google Scholar]
76. Lefebvre C, Rajbhandari P, Alvarez MJ, Bandaru P, Lim WK. 76.  et al. 2010. A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers. Mol. Syst. Biol. 6:377 [Google Scholar]
77. Lettice LA, Heaney SJ, Purdie LA, Li L, de Beer P. 77.  et al. 2003. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum. Mol. Genet. 12:1725–35 [Google Scholar]
78. Lettice LA, Horikoshi T, Heaney SJ, van Baren MJ, van der Linde HC. 78.  et al. 2002. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. PNAS 99:7548–53 [Google Scholar]
79. Li L, He S, Sun JM, Davie JR. 79.  2004. Gene regulation by Sp1 and Sp3. Biochem. Cell Biol. 82:460–71 [Google Scholar]
80. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T. 80.  et al. 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–93 [Google Scholar]
81. Liu XS, Wu H, Ji X, Stelzer Y, Wu X. 81.  et al. 2016. Editing DNA methylation in the mammalian genome. Cell 167:233–47 [Google Scholar]
82. Lupianez DG, Kraft K, Heinrich V, Krawitz P, Brancati F. 82.  et al. 2015. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161:1012–25 [Google Scholar]
83. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA. 83.  et al. 2009. Finding the missing heritability of complex diseases. Nature 461:747–53 [Google Scholar]
84. Matharu N, Ahituv N. 84.  2015. Minor loops in major folds: enhancer-promoter looping, chromatin restructuring, and their association with transcriptional regulation and disease. PLOS Genet 11:e1005640 [Google Scholar]
85. Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E. 85.  et al. 2012. Systematic localization of common disease-associated variation in regulatory DNA. Science 337:1190–95 [Google Scholar]
86. Mele M, Ferreira PG, Reverter F, DeLuca DS, Monlong J. 86.  et al. 2015. The human transcriptome across tissues and individuals. Science 348:660–65 [Google Scholar]
87. Melnikov A, Murugan A, Zhang X, Tesileanu T, Wang L. 87.  et al. 2012. Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay. Nat. Biotechnol. 30:271–77 [Google Scholar]
88. Mifsud B, Tavares-Cadete F, Young AN, Sugar R, Schoenfelder S. 88.  et al. 2015. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat. Genet. 47:598–606 [Google Scholar]
89. Muller HJ. 89.  1930. Types of visible variations induced by X-rays in Drosophila. J. Genet. 22:299–334 [Google Scholar]
90. Mumbach MR, Rubin AJ, Flynn RA, Dai C, Khavari PA. 90.  et al. 2016. HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Nat. Methods 13:919–22 [Google Scholar]
91. Murtha M, Tokcaer-Keskin Z, Tang Z, Strino F, Chen X. 91.  et al. 2014. FIREWACh: high-throughput functional detection of transcriptional regulatory modules in mammalian cells. Nat. Methods 11:559–65 [Google Scholar]
92. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I. 92.  et al. 2012. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–85 [Google Scholar]
93. Ong CT, Corces VG. 93.  2014. CTCF: an architectural protein bridging genome topology and function. Nat. Rev. Genet. 15:234–46 [Google Scholar]
94. Park SL, Cheng I, Pendergrass SA, Kucharska-Newton AM, Lim U. 94.  et al. 2013. Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study. Am. J. Epidemiol. 178:780–90 [Google Scholar]
95. Pasquali L, Gaulton KJ, Rodriguez-Segui SA, Mularoni L, Miguel-Escalada I. 95.  et al. 2014. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat. Genet. 46:136–43 [Google Scholar]
96. Patwardhan RP, Hiatt JB, Witten DM, Kim MJ, Smith RP. 96.  et al. 2012. Massively parallel functional dissection of mammalian enhancers in vivo. Nat. Biotechnol. 30:265–70 [Google Scholar]
97. Patwardhan RP, Lee C, Litvin O, Young DL, Pe'er D, Shendure J. 97.  2009. High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesis. Nat. Biotechnol. 27:1173–75 [Google Scholar]
98. Pennacchio LA, Bickmore W, Dean A, Nobrega MA, Bejerano G. 98.  2013. Enhancers: five essential questions. Nat. Rev. Genet. 14:288–95 [Google Scholar]
99. Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM. 99.  et al. 2013. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat. Methods 10:973–76 [Google Scholar]
100. Phillips JE, Corces VG. 100.  2009. CTCF: master weaver of the genome. Cell 137:1194–211 [Google Scholar]
101. Piovan E, Yu J, Tosello V, Herranz D, Ambesi-Impiombato A. 101.  et al. 2013. Direct reversal of glucocorticoid resistance by AKT inhibition in acute lymphoblastic leukemia. Cancer Cell 24:766–76 [Google Scholar]
102. Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J. 102.  2011. A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470:279–83 [Google Scholar]
103. Rajagopal N, Srinivasan S, Kooshesh K, Guo Y, Edwards MD. 103.  et al. 2016. High-throughput mapping of regulatory DNA. Nat. Biotechnol. 34:167–74 [Google Scholar]
104. Riethoven JJ. 104.  2010. Regulatory regions in DNA: promoters, enhancers, silencers, and insulators. Methods Mol. Biol. 674:33–42 [Google Scholar]
105. Kundaje A, Meuleman W, Ernst J, Bilenky M. 105. Roadmap Epigenom. Consort., et al. 2015. Integrative analysis of 111 reference human epigenomes. Nature 518:317–30 [Google Scholar]
106. Sanjana NE, Wright J, Zheng K, Shalem O, Fontanillas P. 106.  et al. 2016. High-resolution interrogation of functional elements in the noncoding genome. Science 353:1545–49 [Google Scholar]
107. Scuteri A, Sanna S, Chen WM, Uda M, Albai G. 107.  et al. 2007. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLOS Genet 3:e115 [Google Scholar]
108. Sharon E, Kalma Y, Sharp A, Raveh-Sadka T, Levo M. 108.  et al. 2012. Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters. Nat. Biotechnol. 30:521–30 [Google Scholar]
109. Shen SQ, Myers CA, Hughes AE, Byrne LC, Flannery JG, Corbo JC. 109.  2016. Massively parallel cis-regulatory analysis in the mammalian central nervous system. Genome Res 26:238–55 [Google Scholar]
110. Smale ST, Kadonaga JT. 110.  2003. The RNA polymerase II core promoter. Annu. Rev. Biochem. 72:449–79 [Google Scholar]
111. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ. 111.  et al. 2014. Obesity-associated variants within FTO form long-range functional connections with IRX3. . Nature 507:371–75 [Google Scholar]
112. Smith EM, Lajoie BR, Jain G, Dekker J. 112.  2016. Invariant TAD boundaries constrain cell-type-specific looping interactions between promoters and distal elements around the CFTR locus. Am. J. Hum. Genet. 98:185–201 [Google Scholar]
113. Smith RP, Taher L, Patwardhan RP, Kim MJ, Inoue F. 113.  et al. 2013. Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model. Nat. Genet. 45:1021–28 [Google Scholar]
114. Song L, Crawford GE. 114.  2010. DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells. Cold Spring Harb. Protoc 2010:pdb.prot5384 [Google Scholar]
115. Srinivasan L, Atchison ML. 115.  2004. YY1 DNA binding and PcG recruitment requires CtBP. Genes Dev 18:2596–601 [Google Scholar]
116. Stitzel ML, Sethupathy P, Pearson DS, Chines PS, Song L. 116.  et al. 2010. Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Cell Metab 12:443–55 [Google Scholar]
117. Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP. 117.  et al. 2007. Population genomics of human gene expression. Nat. Genet. 39:1217–24 [Google Scholar]
118. Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A. 118.  et al. 2011. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell 147:370–81 [Google Scholar]
119. Tewhey R, Kotliar D, Park DS, Liu B, Winnicki S. 119.  et al. 2016. Direct identification of hundreds of expression-modulating variants using a multiplexed reporter assay. Cell 165:1519–29 [Google Scholar]
120. Tiwari VK, McGarvey KM, Licchesi JD, Ohm JE, Herman JG. 120.  et al. 2008. PcG proteins, DNA methylation, and gene repression by chromatin looping. PLOS Biol 6:2911–27 [Google Scholar]
121. Trynka G, Sandor C, Han B, Xu H, Stranger BE. 121.  et al. 2013. Chromatin marks identify critical cell types for fine mapping complex trait variants. Nat. Genet. 45:124–30 [Google Scholar]
122. Ulirsch JC, Nandakumar SK, Wang L, Giani FC, Zhang X. 122.  et al. 2016. Systematic functional dissection of common genetic variation affecting red blood cell traits. Cell 165:1530–45 [Google Scholar]
123. VanderMeer JE, Ahituv N. 123.  2011. cis-Regulatory mutations are a genetic cause of human limb malformations. Dev. Dyn. 240:920–30 [Google Scholar]
124. Welter D, MacArthur J, Morales J, Burdett T, Hall P. 124.  et al. 2014. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42:D1001–6 [Google Scholar]
125. White MA, Myers CA, Corbo JC, Cohen BA. 125.  2013. Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks. PNAS 110:11952–57 [Google Scholar]