Transcription factor binding at enhancers: Shaping a genomic regulatory landscape in flux

Frontiers in Genetics

Volumn 3, Issue SEP, 2012, Pages

  Palstra, Robert Jan ^a   Grosveld, Frank ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Chromatin looping; Cis regulation; Enhancer; Transcription; Transcription factor

Indexed keywords

EUKARYOTA; MAMMALIA;

EID: 84876093553     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2012.00195     Document Type: Review

References (166)

1. Ahmadiyeh, N., Pomerantz, M. M., Grisanzio, C., Herman, P., Jia, L., Almendro, V., et al. (2010). 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc. Natl. Acad. Sci. U.S.A. 107, 9742-9746.
2. Akhtar-Zaidi, B., Cowper-Sal-Lari, R., Corradin, O., Saiakhova, A., Bartels, C. F., Balasubramanian, D., et al. (2012). Epigenomic enhancer profiling defines a signature of colon cancer. Science 336, 736-739.
3. Albuisson, J., Isidor, B., Giraud, M., Pichon, O., Marsaud, T., David, A., et al. (2011). Identification of two novel mutations in Shh long-range regulator associated with familial pre-axial polydactyly. Clin. Genet. 79, 371-377.
4. Alvarez, M., Rhodes, S. J., and Bid-well, J. P. (2003). Context-dependent transcription: all politics is local. Gene 313, 43-57.
5. Amouyal, M. (1991). The remote control of transcription, DNA looping and DNA compaction. Biochimie 73, 1261-1268.
6. Arnosti, D. N., and Kulkarni, M. M. (2005). Transcriptional enhancers: intelligent enhanceosomes or flexible billboards? J. Cell. Biochem. 94, 890-898.
7. Banerji, J., Olson, L., and Schaffner, W. (1983). A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell 33, 729-740.
8. Banerji, J., Rusconi, S., and Schaffner, W. (1981). Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell 27, 299-308.
9. Barski, A., Cuddapah, S., Cui, K., Roh, T. Y., Schones, D. E., Wang, Z., et al. (2007). High-resolution profiling of histone methylations in the human genome. Cell 129, 823-837.
10. Bell, A. C., West, A. G., and Felsen-feld, G. (1999). The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98,387-396.
11. Bergsland, M., Ramskold, D., Zaouter, C., Klum, S., Sandberg, R., and Muhr, J. (2011). Sequentially acting Sox transcription factors in neural lineage development. Genes Dev. 25, 2453-2464.
12. Bernstein, B. E., Stamatoyannopoulos, J. A., Costello, J. F., Ren, B., Milosavljevic, A., Meissner, A., et al. (2010). The NIH Roadmap Epigenomics Mapping Consortium. Nat. Biotechnol. 28,1045-1048.
13. Blow, M. J., Mcculley, D. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., et al. (2010). ChIP-Seq identification of weakly conserved heart enhancers. Nat. Genet. 42,806-810.
14. Bogdanovic, O., Fernandez-Minan, A., Tena, J. J., De Lacalle-Mustienes, E., Hidalgo, C., Van Kruysbergen, I., et al. (2012). Dynamics of enhancer chromatin signatures mark the transition from pluripotency to cell specification during embryogenesis. Genome Res. doi: 10.1101/gr.134833.111 [Epub ahead of print].
15. Bonn, S., Zinzen, R. P., Girardot, C., Gustafson, E. H., Perez-Gonzalez, A., Delhomme, N., et al. (2012). Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development. Nat. Genet. 44, 148-156.
16. Enhancers as information integration hubs in development: lessons from genomics
17. Carter, D., Chakalova, L., Osborne, C. S., Dai, Y. F., and Fraser, P. (2002). Long-range chromatin regulatory interactions in vivo. Nat. Genet. 32,623-626.
18. Chepelev, I., Wei, G., Wangsa, D., Tang, Q., and Zhao, K. (2012). Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization. Cell Res. 22, 490-503.
19. Chien, R., Zeng, W., Kawauchi, S., Bender, M. A., Santos, R., Gregson, H. C., et al. (2012). Cohesin mediates chromatin interactions that regulate mammalian {beta}-globin expression.J. Biol Chem. 286,17870-17878.
20. Chopra, V. S., Cande, J., Hong, J. W., and Levine, M. (2009). Stalled Hox promoters as chromosomal boundaries. Genes Dev. 23, 1505-1509.
21. Chopra, V. S., Kong, N., and Levine, M. (2012). Transcriptional repression via antilooping in the Drosophila embryo. Proc. Natl. Acad. Sci. U.S.A. 109, 9460-9464.
22. Chorley, B. N., Wang, X., Campbell, M. R., Pittman, G. S., Noureddine, M. A., and Bell, D. A. (2008). Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: current and developing technologies. Mutat. Res. 659, 147-157.
23. Chuang, C. H., Carpenter, A. E., Fuchsova, B., Johnson, T., De Lanerolle, P., and Belmont, A. S. (2006). Long-range directional movement of an interphase chromosome site. Curr. Biol. 16, 825-831.
24. Consortium, G. P. (2010). A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073.
25. Cotney, J., Leng, J., Oh, S., Demare, L. E., Reilly, S. K., Gerstein, M. B., et al. (2012). Chromatin state signatures associated with tissue-specific gene expression and enhancer activity in the embryonic limb. Genome Res. 22, 1069-1080.
26. Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., et al. (2010). Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. U.S.A. 107,21931-21936.
27. De Santa, F., Barozzi, I., Mietton, F., Ghisletti, S., Polletti, S., Tusi, B. K., et al. (2010). A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol. 8, e1000384. doi: 10.1371/journal.pbio. 1000384
28. de Wit, E., and de Laat, W. (2012). A decade of 3C technologies: insights into nuclear organization. Genes Dev. 26, 11-24.
29. Degner, J. F., Pai, A. A., Pique-Regi, R., Veyrieras, J. B., Gaffney, D. J., Pickrell, J. K., et al. (2012). DNase I sensitivity QTLs are a major determinant of human expression variation. Nature 482,390-394.
30. Dekker, J., Rippe, K., Dekker, M., and Kleckner, N. (2002). Capturing chromosome conformation. Science 295, 1306-1311.
31. Deng, B., Melnik, S., and Cook, P. R. (2012a). Transcription factories, chromatin loops, and the dys-regulation of gene expression in malignancy. Semin. Cancer Biol. doi: 10.1016/j.semcancer.2012.01.003 [Epub ahead of print].
32. Deng, W., Lee, J., Wang, H., Miller, J., Reik, A., Gregory, P. D., et al. (2012b). Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell 149, 1233-1244.
33. Dillon, N., Trimborn, T., Strouboulis, J., Fraser, P., and Grosveld, E (1997). The effect of distance on long-range chromatin interactions. Mol. Cell 1, 131-139.
34. Disanto, G., Sandve, G. K., Berlanga-Taylor, A. J., Morahan, J. M., Dobson, R., Giovannoni, G., et al. (2012). Genomic regions associated with multiple sclerosis are active in B cells. PLoS ONE 7, e32281. doi: 10.1371/journal.pone.0032281
35. Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., et al. (2012). Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380.
36. Dorsett, D. (2011). Cohesin: genomic insights into controlling gene transcription and development. Curr. Opin. Genet. Dev. 21,199-206.
37. Drissen, R., Palstra, R. J., Gillemans, N., Splinter, E., Grosveld, E, Philipsen, S., et al. (2004). The active spatial organization of the beta-globin locus requires the transcription factor EKLF. Genes Dev. 18, 2485-2490.
38. Du, M. J., Lv, X., Hao, D. L., Zhao, G. W., Wu, X. S., Wu, F., et al. (2008). MafK/NF-E2 p18 is required for beta-globin genes activation by mediating the proximity of LCR and active beta-globin genes in MEL cell line. Int. J. Biochem. Cell Biol. 40, 1481-1493.
39. Dundr, M., Ospina, J. K., Sung, M. H., John, S., Upender, M., Ried, T., et al. (2007). Actin-dependent intranuclear repositioning of an active gene locus in vivo. J. Cell Biol. 179, 1095-1103.
40. Ellis, J., Tan-Un, K. C., Harper, A., Michalovich, D., Yannoutsos, N., Philipsen, S., et al. (1996). A dominant chromatin-opening activity in 5' hypersensitive site 3 of the human beta-globin locus control region. EMBO J. 15, 562-568.
41. Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B., et al. (2011). Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43-49.
42. Erokhin, M., Davydova, A., Kyrchanova, O., Parshikov, A., Georgiev, P., and Chetverina, D. (2011). Insulators form gene loops by interacting with promoters in Drosophila. Development 138, 4097-4106.
43. Feng, Y Q., Warin, R., Li, T., Olivier, E., Besse, A., Lobell, A., et al. (2005). The human beta-globin locus control region can silence as well as activate gene expression. Mol. Cell. Biol. 25, 3864-3874.
44. Ferrai, C., Naum-Ongania, G., Longo-bardi, E., Palazzolo, M., Disanza, A., Diaz, V. M., et al. (2009). Induction of HoxB transcription by retinoic acid requires actin polymerization. Mol. Biol. Cell 20, 3543-3551.
45. Fujioka, M., Wu, X., and Jaynes, J. B. (2009). A chromatin insulator mediates transgene homing and very long-range enhancer-promoter communication. Development 136, 3077-3087.
46. [1000] Genomes Project Consortium. (2010). A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073.
47. Giresi, P. G., Kim, J., Mcdaniell, R. M., Iyer, V. R., and Lieb, J. D. (2007). FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Res. 17, 877-885.
48. Grosveld, F., Van Assendelft, G. B., Greaves, D. R., and Kollias, G. (1987). Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell 51,975-985.
49. Haering, C. H., and Jessberger, R. (2012). Cohesin in determining chromosome architecture. Exp. Cell Res. 318,1386-1393.
50. Hamada, H. (1986). Random isolation of gene activator elements from the human genome. Mol. Cell. Biol. 6, 4185-4194.
51. Handoko, L., Xu, H., Li, G., Ngan, C. Y., Chew, E., Schnapp, M., et al. (2011). CTCF-mediated functional chromatin interactome in pluripo-tent cells. Nat. Genet. 43, 630-638.
52. Hanscombe, O., Whyatt, D., Fraser, P., Yannoutsos, N., Greaves, D., Dillon, N., et al. (1991). Importance of globin gene order for correct developmental expression. Genes Dev. 5, 1387-1394.
53. Harismendy, O., Notani, D., Song, X., Rahim, N. G., Tanasa, B., Heintzman, N., et al. (2011). 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response. Nature 470, 264-268.
54. Hawkins, R. D., Hon, G. C., and Ren, B. (2010). Next-generation genomics: an integrative approach. Nat. Rev. Genet. 11,476-486.
55. Hayday, A. C., Gillies, S. D., Saito, H., Wood, C., Wiman, K., Hayward, W. S., et al. (1984). Activation of a translocated human c-myc gene by an enhancer in the immunoglobu-lin heavy-chain locus. Nature 307, 334-340.
56. He, A., Kong, S. W., Ma, Q., and Pu, W. T. (2011). Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart. Proc. Natl. Acad. Sci. U.S.A. 108,5632-5637.
57. Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., et al. (2009). Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459,108-112.
58. Heintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., et al. (2007). Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39, 311-318.
59. Herold, M., Bartkuhn, M., and Renkawitz, R. (2012). CTCF: insights into insulator function during development. Development 139, 1045-1057.
60. Hesselberth, J. R., Chen, X., Zhang, Z., Sabo, P. J., Sandstrom, R., Reynolds, A. P., et al. (2009). Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nat. Methods 6, 283-289.
61. Hoffman, M. M., Buske, O. J., Wang, J., Weng, Z., Bilmes, J. A., and Noble, W. S. (2012). Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nat. Methods 9, 473-476.
62. Hu, Q., Kwon, Y. S., Nunez, E., Cardamone, M. D., Hutt, K. R., Ohgi, K. A., et al. (2008). Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD 1-dependent gene networking in interchromatin granules. Proc. Natl. Acad. Sci. U.S.A. 105, 19199-19204.
63. Jing, H., Vakoc, C. R., Ying, L., Man-dat, S., Wang, H., Zheng, X., et al. (2008). Exchange of GATA factors mediates transitions in looped chromatin organization at a developmen-tally regulated gene locus. Mol. Cell 29 232-242.
64. Johnson, D. S., Mortazavi, A., Myers, R. M., and Wold, B. (2007). Genome-wide mapping of in vivo protein-DNA interactions. Science 316, 1497-1502.
65. Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., Van Berkum,N. L.,et al. (2010). Mediator and cohesin connect gene expression and chromatin architecture. Nature 467, 430-435.
66. Kasowski, M., Grubert, F., Heffelfin-ger, C., Hariharan, M., Asabere, A., Waszak, S. M., et al. (2010). Variation in transcription factor binding among humans. Science 328, 232-235.
67. Kellner, W A., Ramos, E., Van Bor-tle, K., Takenaka, N., and Corces, V G. (2012). Genome-wide phos-phoacetylation of histone H3 at Drosophila enhancers and promoters. Genome Res. 22, 1081-1088.
68. Kim, S. I., Bultman, S. J., Kiefer, C. M., Dean, A., and Bresnick, E. H. (2009). BRG1 requirement for long-range interaction of a locus control region with a downstream promoter. Proc. Natl. Acad. Sci. U.S.A. 106, 2259-2264.
69. Kim, T. K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., et al. (2010). Widespread transcription at neuronal activity-regulated enhancers. Nature 465, 182-187.
70. Kioussis, D., Vanin, E., Delange, T., Flavell, R. A., and Grosveld, F. G. (1983). Beta-globin gene inactiva-tion by DNA translocation in gamma beta-thalassaemia. Nature 306, 662-666.
71. Kleinjan, D. A., andLettice,L. A. (2008). Long-range gene control and genetic disease. Adv. Genet. 61, 339-388.
72. Koch, F., Fenouil, R., Gut, M., Cauchy, P., Albert, T. K., Zacarias-Cabeza, J., et al. (2011). Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Nat. Struct. Mol. Biol. 18, 956-963.
73. Kooren, J., Palstra, R. J., Klous, P., Splinter, E., Von Lindern, M., Grosveld, E, et al. (2007). Beta-globin active chromatin Hub formation in differentiating erythroid cells and in p45 NF-E2 knock-out mice. J. Biol. Chem. 282,16544-16552.
74. Korostowski, L., Raval, A., Breuer, G., and Engel, N. (2011). Enhancer-driven chromatin interactions during development promote escape from silencing by a long non-coding RNA. Epigenetics Chromatin 4, 21.
75. Kowalczyk, M. S., Hughes, J. R., Gar-rick, D., Lynch, M. D., Sharpe, J. A., Sloane-Stanley, J. A., et al. (2012). Intragenic enhancers act as alternative promoters. Mol. Cell 45, 447-458.
76. Krebs, A. R., Karmodiya, K., Lindahl-Allen, M., Struhl, K., and Tora, L. (2011). SAGA and ATAC histone acetyl transferase complexes regulate distinct sets of genes and ATAC defines a class of p300-independent enhancers. Mol. Cell 44,410-423.
77. Kvon, E. Z., Stampfel, G., Yanez-Cuna, J. O., Dickson, B. J., and Stark, A. (2012). HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature. Genes Dev. 26,908-913.
78. Lan, X., Witt, H., Katsumura, K., Ye, Z., Wang, Q., Bresnick, E. H., et al. (2012). Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages. Nucleic Acids Res. 40, 7690-7704.
79. Laurell, T., Vandermeer, J. E., Wenger, A. M., Grigelioniene, G., Norden-skjold, A., Arner, M., et al. (2012). A novel 13 base pair insertion in the sonic hedgehog ZRS limb enhancer (ZRS/LMBR1) causes preaxial poly-dactyly with triphalangeal thumb. Hum. Mutat. 33,1063-1066.
80. Leach, K. M., Nightingale, K., Igarashi, K., Levings, P. P., Engel, J. D., Becker, P. B., et al. (2001). Reconstitution of human beta-globin locus control region hypersensitive sites in the absence of chromatin assembly. Mol. Cell. Biol. 21,2629-2640.
81. Li, G., Ruan, X., Auerbach, R. K., Sandhu, K. S., Zheng, M., Wang, P., et al. (2012). Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148, 84-98.
82. Lieberman-Aiden, E., Van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., et al. (2009). Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289-293.
83. Liu, Z., Scannell, D. R., Eisen, M. B., and Tjian, R. (2011). Control of embryonic stem cell lineage commitment by core promoter factor, TAF3. Cell 146, 720-731.
84. Maksimenko, O., Golovnin, A., and Georgiev, P. (2008). Enhancer-promoter communication is regulated by insulator pairing in a Drosophila model bigenic locus. Mol. Cell. Biol. 28, 5469-5477.
85. Maston, G. A., Landt, S. G., Snyder, M., and Green, M. R. (2012). Characterization of enhancer function from genome-wide analyses. Annu. Rev. GenomicsHum. Genet. 13,29-57.
86. Matthews, J. M., and Visvader, J. E. (2003). LIM-domain-binding protein 1: a multifunctional cofactor that interacts with diverse proteins. EMBORep. 4, 1132-1137.
87. May, D., Blow, M. J., Kaplan, T., Mccul-ley, D. J., Jensen, B. C., Akiyama, J. A., et al. (2011). Large-scale discovery of enhancers from human heart tissue. Nat. Genet. 44, 89-93.
88. McCord, R. P., Zhou, V W, Yuh, T., and Bulyk, M. L. (2011). Distant cis-regulatory elements in human skeletal muscle differentiation. Genomics 98,401-411.
89. Meireles-Filho, A. C., and Stark, A. (2009). Comparative genomics of gene regulation-conservation and divergence of cis-regulatory information. Curr. Opin. Genet. Dev. 19, 565-570.
90. Melgar, M. F., Collins, F. S., and Sethupathy, P. (2011). Discovery of active enhancers through bidirectional expression of short transcripts. Genome Biol. 12,R113.
91. Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., et al. (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553-560.
92. Mikkelsen, T. S., Xu, Z., Zhang, X., Wang, L., Gimble, J. M., Lander, E. S., et al. (2010). Comparative epige-nomic analysis of murine and human adipogenesis. Cell 143,156-169.
93. Milot, E., Strouboulis, J., Trimborn, T., Wijgerde, M., De Boer, E., Langeveld, A., et al. (1996). Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription. Cell 87, 105-114.
94. Mitchell, J. A., and Fraser, P. (2008). Transcription factories are nuclear subcompartments that remain in the absence of transcription. Genes Dev. 22,20-25.
95. Miyamoto, K., Pasque, V., Jullien, J., and Gurdon, J. B. (2012). Nuclear actin polymerization is required for transcriptional reprogramming of Oct4 by oocytes. Genes Dev. 25, 946-958.
96. Musunuru, K., Strong, A., Frank-Kamenetsky, M., Lee, N. E., Ahfeldt, T., Sachs, K. V., et al. (2010). From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466, 714-719.
97. Nechaev, S., and Adelman, K. (2011). Pol II waiting in the starting gates: regulating the transition from transcription initiation into productive elongation. Biochim. Biophys. Acta 1809, 34-45.
98. Ong, C. T., and Corces, V. G. (2012). Enhancers: emerging roles in cell fate specification. EMBO Rep. 13, 423-430.
99. Orom, U. A., Derrien, T., Beringer, M., Gumireddy, K., Gardini, A., Bussotti, G., et al. (2010). Long noncoding RNAs with enhancer-like function in human cells. Cell 143, 46-58.
100. Orom, U. A., and Shiekhattar, R. (2011). Noncoding RNAs and enhancers: complications of a long-distance relationship. Trends Genet. 27, 433-439.
101. Palstra, R. J., Simonis, M., Klous, P., Brasset, E., Eijkelkamp, B., and De Laat, W. (2008). Maintenance of long-range DNA interactions after inhibition of ongoing RNA polymerase II transcription. PLoS ONE 3, e1661. doi: 10.1371/jour-nal.pone.0001661
102. Palstra, R. J., Tolhuis, B., Splinter, E., Nijmeijer, R., Grosveld, F., and De Laat, W. (2003). The beta-globin nuclear compartment in development and erythroid differentiation. Nat. Genet. 35,190-194.
103. Papantonis, A., and Cook, P. R. (2010). Genome architecture and the role of transcription. Curr. Opin. Cell Biol. 22,271-276.
104. Parelho, V., Hadjur, S., Spivakov, M., Leleu, M., Sauer, S., Gregson, H. C., et al. (2008). Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 132, 422-433.
105. Pekowska, A., Benoukraf, T., Zacarias-Cabeza, J., Belhocine, M., Koch, F., Holota, H., et al. (2011). H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J.30,4198-4210.
106. Petrykowska, H. M., Vockley, C. M., and Elnitski, L. (2008). Detection and characterization of silencers and enhancer-blockers in the greater CFTR locus. Genome Res. 18, 1238-1246.
107. Pham, T. H., Benner, C., Lichtinger, M., Schwarzfischer, L., Hu, Y., Andreesen, R., et al. (2012). Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states. Blood 119, e161-e171.
108. Pomerantz, M. M., Ahmadiyeh, N., Jia, L., Herman, P., Verzi, M. P., Dodda-paneni, H., et al. (2009). The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat. Genet. 41, 882-884.
109. Raab, J. R., Chiu, J., Zhu, J., Katzman, S., Kurukuti, S., Wade, P. A., et al. (2011). Human tRNA genes function as chromatin insulators. EMBO J. 31, 330-350.
110. Raab, J. R., and Kamakaka, R. T. (2010). Insulators and promoters: closer than we think. Nat. Rev. Genet. 11, 439-446.
111. Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., and Wysocka, J. (2011). A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470, 279-283.
112. Rahimov, F., Marazita, M. L., Visel, A., Cooper, M. E., Hitchler, M. J., Rubini, M., et al. (2008). Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat. Genet. 40, 1341-1347.
113. Ram, O., Goren, A., Amit, I., Shoresh, N., Yosef, N., Ernst, J., et al. (2011). Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells. Cell 147, 1628-1639.
114. Reddy, T. E., Gertz, J., Pauli, F., Kucera, K. S., Varley, K. E., Newberry, K. M., et al. (2012). Effects of sequence variation on differential allelic transcription factor occupancy and gene expression. Genome Res. 22,860-869.
115. Ren, X., Siegel, R., Kim, U., and Roeder, R. G. (2011). Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication. Mol. Cell 42, 342-355.
116. Robertson, G., Hirst, M., Bainbridge, M., Bilenky, M., Zhao, Y., Zeng, T., et al. (2007). Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing. Nat. Methods 4, 651-657.
117. Rodin, S., Kyrchanova, O., Pomer-antseva, E., Parshikov, A., and Georgiev, P. (2007). New properties of Drosophila fab-7 insulator. Genetics 177,113-121.
118. Royo, J. L., Hidalgo, C., Roncero, Y., Seda, M. A., Akalin, A., Lenhard, B., et al. (2011). Dissecting the tran-scriptional regulatory properties of human chromosome 16 highly conserved non-coding regions. PLoS ONE 6, e24824. doi: 10.1371/jour-nal.pone.0024824
119. Rubio, E. D., Reiss, D. J., Welcsh, P. L., Disteche, C. M., Filippova, G. N., Baliga, N. S., et al. (2008). CTCF physically links cohesin to chromatin. Proc. Natl. Acad. Sci. U.S.A. 105, 8309-8314.
120. Sabo, P. J., Kuehn, M. S., Thurman, R., Johnson, B. E., Johnson, E. M., Cao, H., et al. (2006). Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nat. Methods 3, 511-518.
121. Sawado, T., Halow, J., Bender, M. A., and Groudine, M. (2003). The beta-globin locus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation. Genes Dev. 17, 1009-1018.
122. Schnetz, M. P., Bartels, C. F., Shastri, K., Balasubramanian, D., Zentner, G. E., Balaji, R., et al. (2009). Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res. 19,590-601.
123. Schnetz, M. P., Handoko, L., Akhtar-Zaidi, B., Bartels, C. F., Pereira, C. E, Fisher, A. G., et al. (2010). CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression. PLoS Genet. 6, e1001023. doi: 10.1371/journal.pgen.1001023
124. Sheng, Y., and Previti, C. (2011). Genomic features and computational identification of human microRNAs under long-range developmental regulation. BMC Genomics 12, 270. doi: 10.1186/1471-2164-12-270
125. Simms, T. A., Dugas, S. L., Gremillion, J. C., Ibos, M. E., Dandurand, M. N., Toliver, T. T., et al. (2008). TFIIIC binding sites function as both heterochromatin barriers and chromatin insulators in Saccharomyces cerevisiae. Eukaryot. Cell 7, 2078-2086.
126. Soler, E., Andrieu-Soler, C., De Boer, E., Bryne, J. C., Thongjuea, S., Stadhouders, R., et al. (2010). The genome-wide dynamics of the binding of Ldb 1 complexes during erythroid differentiation. Genes Dev. 24,277-289.
127. Song, S. H., Hou, C., and Dean, A. (2007). A positive role for NLI/Ldb1 in long-range beta-globin locus control region function. Mol. Cell 28, 810-822.
128. Soshnev, A. A., Li, X., Wehling, M. D., and Geyer, P. K. (2008). Context differences reveal insulator and activator functions of a Su(Hw) binding region. PLoS Genet. 4, e1000159. doi: 10.1371/journal.pgen.1000159
129. Spilianakis, C. G., and Flavell, R. A. (2004). Long-range intrachromosomal interactions in the T helper type 2 cytokine locus. Nat. Immunol. 5, 1017-1027.
130. Splinter, E., Heath, H., Kooren, J., Palstra, R. J., Klous, P., Grosveld, F., et al. (2006). CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. Genes Dev. 20, 2349-2354.
131. Stadhouders, R., Thongjuea, S., Andrieu-Soler, C., Palstra, R. J., Bryne, J. C., Van Den Heuvel, A., et al. (2011). Dynamic long-range chromatin interactions control Myb proto-oncogene transcription during erythroid development. EMBOJ. 31, 986-999.
132. Svotelis, A., Bianco, S., Madore, J., Huppe, G., Nordell-Markovits, A., Mes-Masson, A. M., et al. (2011). H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERalpha lig-and dependency. EMBO J. 30, 3947-3961.
133. Taberlay, P. C., Kelly, T. K., Liu, C. C., You, J. S., De Carvalho, D. D., Miranda, T. B., et al. (2011). Polycomb-repressed genes have permissive enhancers that initiate reprogramming. Cell 147, 1283-1294.
134. Tan, M., Luo, H., Lee, S., Jin, F., Yang, J. S., Montellier, E., et al. (2011). Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146,1016-1028.
135. Taramelli, R., Kioussis, D., Vanin, E., Bartram, K., Groffen, J., Hurst, J., et al. (1986). Gamma delta beta-thalassaemias 1 and 2 are the result of a 100 kbp deletion in the human beta-globin cluster. Nucleic Acids Res. 14,7017-7029.
136. Tartof, K. D., and Henikoff, S. (1991). Transsensing effects from Drosophila to humans. Cell 65, 201-203.
137. Taslim, C., Chen, Z., Huang, K., Huang, T. H., Wang, Q., and Lin, S. (2012). Integrated analysis identifies a class of androgen-responsive genes regulated by short combinatorial long-range mechanism facilitated by CTCF. Nucleic Acids Res. 40, 4754-4764.
138. Teng, L., Firpi, H. A., and Tan, K. (2011). Enhancers in embryonic stem cells are enriched for transposable elements and genetic variations associated with cancers. Nucleic Acids Res. 39,7371-7379.
139. Thanos, D., and Maniatis, T. (1995). Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell 83, 1091-1100.
140. Tolhuis, B., Palstra, R. J., Splinter, E., Grosveld, F., and De Laat, W. (2002). Looping and interaction between hypersensitive sites in the active beta-globin locus. Mol. Cell 10, 1453-1465.
141. Tuan, D., Kong, S., and Hu, K. (1992). Transcription of the hypersensitive site HS2 enhancer in erythroid cells. Proc. Natl. Acad. Sci. U.S.A. 89, 11219-11223.
142. Tuan, D., Solomon, W., Li, Q., and London, I. M. (1985). The "beta-like-globin" gene domain in human erythroid cells. Proc. Natl. Acad. Sci. U.S.A. 82,6384-6388.
143. Vakoc, C. R., Letting, D. L., Gheldof, N., Sawado, T., Bender, M. A., Groudine, M., et al. (2005). Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1. Mol. Cell 17, 453-462.
144. Vernimmen, D., Lynch, M. D., De Gobbi, M., Garrick, D., Sharpe, J. A., Sloane-Stanley, J. A., et al. (2011). Polycomb eviction as a new distant enhancer function. Genes Dev. 25, 1583-1588.
145. Vieira, K. F., Levings, P. P., Hill, M. A., Crusselle, V. J., Kang, S. H., Engel, J. D., et al. (2004). Recruitment of transcription complexes to the beta-globin gene locus in vivo and in vitro. J. Biol. Chem. 279, 50350-50357.
146. Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama,J.A.,Holt,A., et al. (2009a). ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457,854-858.
147. Visel, A., Rubin, E. M., and Pennacchio,L.A. (2009b). Genomic views of distant-acting enhancers. Nature 461, 199-205.
148. Visser, M., Kayser, M., and Palstra, R. J. (2012). HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res. 22,446-455.
149. Wadman, I. A., Osada, H., Grutz, G. G., Agulnick, A. D., Westphal, H., Forster, A., et al. (1997). The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1andLdb1/NLI proteins. EMBOJ. 16, 3145-3157.
150. Wang, D., Garcia-Bassets, I., Benner, C., Li, W., Su, X., Zhou, Y., et al. (2011). Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474, 390-394.
151. Wang, Z., Zang, C., Rosenfeld, J. A., Schones, D. E., Barski, A., Cuddapah, S., et al. (2008). Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet. 40, 897-903.
152. Wendt, K. S., and Peters, J. M. (2009). How cohesin and CTCF cooperate in regulating gene expression. Chromosome Res. 17,201-214.
153. Wendt, K. S., Yoshida, K., Itoh, T., Bando, M., Koch, B., Schirghuber, E., et al. (2008). Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 451, 796-801.
154. West, A. G., and Fraser, P. (2005). Remote control of gene transcription. Hum. Mol. Genet. 14(Suppl. 1), R101-R111.
155. Weth, O., and Renkawitz, R. (2011). CTCF function is modulated by neighboring DNA binding factors. Biochem. Cell Biol. 89, 459-468.
156. Whyte, W. A., Bilodeau, S., Orlando, D. A., Hoke, H. A., Frampton, G. M., Foster, C. T., et al. (2012). Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. Nature 482, 221-225.
157. Wiench, M., John, S., Baek, S., Johnson, T. A., Sung, M. H., Escobar, T., et al. (2011). DNA methylation status predicts cell type-specific enhancer activity. EMBOJ. 30, 3028-3039.
158. Wright, J. B., Brown, S. J., and Cole, M. D. (2010). 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. 30,1411-1420.
159. Wright, S., Rosenthal, A., Flavell, R., and Grosveld, F. (1984). DNA sequences required for regulated expression of beta-globin genes in murine erythroleukemia cells. Cell 38, 265-273.
160. Wu, C. (1980). The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature 286,854-860.
161. Yoo, E. J., Cooke, N. E., and Liebhaber, S. A. (2012). An RNA-independent linkage of noncoding transcription to long-range enhancer function. Mol. Cell. Biol. 32,2020-2029.
162. Zentner, G. E., Tesar, P. J., and Scacheri, P. C. (2011). Epigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions. Genome Res. 21, 1273-1283.
163. Zhang, X., Cowper-Sal Lari, R., Bailey, S. D., Moore, J. H., and Lupien, M. (2012). Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus. Genome Res. 22, 1437-1446.
164. Zhou, X., Baron, R. M., Hardin, M., Cho, M. H., Zielinski, J., Hawrylkiewicz, I., et al. (2012). Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP. Hum. Mol. Genet. 21, 1325-1335.
165. Zhu, X., Ling, J., Zhang, L., Pi, W., Wu, M., and Tuan, D. (2007). A facilitated tracking and transcription mechanism of long-range enhancer function. Nucleic Acids Res. 35, 5532-5544.
166. Zhu, Y., Van Essen, D., and Saccani, S. (2012). Cell-type-specific control of enhancer activity by H3K9 trimethylation. Mol. Cell 46, 408-423.