Chromatin remodeling effects on enhancer activity

Cellular and Molecular Life Sciences

Volumn 73, Issue 15, 2016, Pages 2897-2910

  García González, Estela ^a   Escamilla Del Arenal, Martín ^b   Arzate Mejía, Rodrigo ^a   Recillas Targa, Félix ^a  

^a INSTITUTO DE FISIOLOGÍA CELULAR   (Mexico)

^b Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

Chromatin; CTCF; Enhancer; Enhancer RNA; Histone modifications; Non coding RNAs; Promoter; Topological associating domains

Indexed keywords

HISTONE; HISTONE ACETYLTRANSFERASE; HISTONE H3; LONG UNTRANSLATED RNA; TRANSCRIPTION FACTOR;

CHROMATIN ASSEMBLY AND DISASSEMBLY; COMPLEX FORMATION; DNA METHYLATION; ENHANCER REGION; ENZYME ACTIVITY; ENZYME ASSAY; EPIGENETICS; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; HISTONE MODIFICATION; HUMAN; MOLECULAR DYNAMICS; NONHUMAN; NUCLEOSOME; REGULATORY MECHANISM; REVIEW; SEQUENCE ANALYSIS; ANIMAL; GENETIC EPIGENESIS; GENETICS; HISTONE CODE; METABOLISM; PROMOTER REGION; TRANSCRIPTION INITIATION;

ANIMALS; CHROMATIN ASSEMBLY AND DISASSEMBLY; DNA METHYLATION; ENHANCER ELEMENTS, GENETIC; EPIGENESIS, GENETIC; HISTONE CODE; HUMANS; PROMOTER REGIONS, GENETIC; RNA, LONG NONCODING; TRANSCRIPTION FACTORS; TRANSCRIPTIONAL ACTIVATION;

EID: 84962295744     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-016-2184-3     Document Type: Review

References (160)

1. Khoury G, Gruss P (1983) Enhancer elements. Cell 33:313–314
2. Banerji J, Rusconi S, Schaffner W (1981) Expression of a β-globin gene is enhanced by remote SV40 DNA sequences. Cell 27:299–308
3. Banerji J, Olson L, Schaffner W (1983) A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell 33:729–740
4. Gillies SD, Morrison SL, Oi VT, Tonegawa S (1983) A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33:717–728
5. Walker MD, Edlund T, Boulet AM, Rutter WJ (1983) Cell-specific expression controlled by the 5′-flanking region of insulin and chymotrypsin genes. Nature 306:557–561
6. Edlund T, Walker MD, Barr PJ, Rutter WJ (1985) Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5′ flanking elements. Science 230:912–916
7. Goodbourn S, Zinn K, Maniatis T (1985) Human β-interferon gene expression is regulated by an inducible enhancer element. Cell 41:509–520
8. Schöler HR, Gruss P (1985) Cell type-specific transcriptional enhancement in vitro requires the presence of trans-acting factors. EMBO J 4:3305–3313
9. Ko MSH, Nakauchi H, Takahashi N (1990) The dose dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates. EMBO J 9:2835–2842
10. Walters MC, Fiering S, Eidemiller J, Magis W, Groudine M, Martin DIK (1995) Enhancers increase the probability but not the level of gene expression. Proc Natl Acad Sci USA 92:7125–7129
11. Sutherland HGE, Martin DIK, Whitelaw E (1997) A globin enhancer acts by increasing the proportion of erythrocytes expressing a linked transgene. Mol Cell Biol 3:1607–1614
12. Yie J, Senger K, Thanos D (1999) Mechanism by which the IFN-β enhanceosome activates transcription. Proc Natl Acad Sci USA 96:13108–13113
13. Sandaltzopoulos R, Becker PB (1998) Heat shock increases the reinitiation rate from potentiated chromatin templates. Mol Cell Biol 18:361–367
14. Chepelev I, Wei G, Wangsa D, Tang Q, 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
15. Bulger M, Groudine M (2011) Functional and mechanistic diversity of distal transcription enhancers. Cell 144:327–339
16. Ong CT, Corces VG (2011) Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet 12:283–293
17. De Laat W, Duboule D (2013) Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502:499–506
18. Calo E, Wysocka J (2013) Modification of enhancer chromatin: what, how and why? Mol Cell 49:825–837
19. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39:311–318
20. Welboren WJ, van Driel MA, Janssen-Megens EM, van Heeringen SJ, Sweep FC, Span PN et al (2009) ChIP-Seq of ERalpha and RNA polymerase II defines genes differentially responding to ligands. EMBO J 28:1418–1428
21. Soufi A, Donahue G, Zaret KS (2012) Facilitators and impediments of the pluripotency reprogramming factors’ initial engagement with the genome. Cell 151:994–1004
22. Spitz F, Furlong EE (2012) Transcription factors: from enhancer binding to developmental control. Nat Rev Genet 13:613–626
23. Soufi A, Garcia MF, Jaroszewicz A, Osman N, Pellegrini M, Zaret KS (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161:555–568
24. Arnosti DN, Kulkarni MM (2005) Transcriptional enhancers: intelligent enhanceosomes or flexible billboards? J Cell Biochem 94:890–898
25. Merika M, Williams AJ, Chen G, Collins T, Thanos D (1998) Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription. Mol Cell 1:277–287
26. Panne D (2008) The enhaceosome. Curr Opin Struct Biol 18:236–242
27. Vega VB, Lin CY, Lai KS, Kong SL, Xie M, Su X et al (2006) Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites. Genome Biol 7:R82
28. Joseph R, Orlov YL, Huss M, Sun W, Kong SL, Ukil L et al (2010) Integrative model of genomic factors for determining binding site selection by estrogen receptor-α. Mol Syst Biol 6:456
29. Zaret KS, Carroll JS (2011) Pioneer transcription factors: establishing competence for gene expression. Genes Dev 25:2227–2241
30. Siersbæk R, Rabiee A, Nielsen R, Sidoli S, Traynor S, Loft A et al (2014) Transcription factor cooperativity in early adipogenic hotspots and super-enhancers. Cell Rep 7:1443–1455
31. Adams CC, Workman JL (1995) Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative. Mol Cell Biol 15:1405–1421
32. Bell O, Tiwari VK, Thomä NH, Schübeler D (2011) Determinants and dynamics of genome accessibility. Nat Rev Genet 12:554–564
33. Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317–330
34. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
35. Iwafuchi-Doi M, Zaret KS (2014) Pioneer transcription factors in cell reprogramming. Genes Dev 28:2679–2692
36. You JS, Kelly TK, De Carvalho DD, Taberlay PC, Liang G, Jones PA (2011) OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes. Proc Natl Acad Sci USA 108:14497–14502
37. Sammons MA, Zhu J, Drake AM, Berger SL (2014) TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity. Genome Res 25:179–188
38. Smith E, Shilatifard A (2014) Enhancer biology and enhanceropathies. Nat Struct Mol Biol 21:210–219
39. Taberlay PC, Kelly TK, Liu CC, You JS, De Carvalho DD, Miranda TB et al (2011) Polycomb-repressed genes have permissive enhancers that initiate reprogramming. Cell 147:1283–1294
40. Malik S, Roeder RG (2005) Dynamic regulation of Pol II transcription by the mammalian Mediator complex. Trends Biochem Sci 30:256–263
41. Weake VM, Workman JL (2010) Inducible gene expression: diverse regulatory mechanisms. Nat Rev Genet 11:426–437
42. Vignali M, Hassan AH, Neely KE, Workman JL (2000) ATP-dependent chromatin remodeling complexes. Mol Cell Biol 5:1899–1910
43. Näär AM, Lemon BD, Tijan R (2001) Transcriptional coactivator complexes. Annu Rev Biochem 70:475–501
44. Becker PB, Hörz W (2002) ATP-dependent nucleosome remodeling. Annu Rev Biochem 71:247–273
45. ENCODE Project Consortium et al (2007) Identification and analysis of functional elements in 1 % of the human genome by the ENCODE pilot project. Nature 447:799–816
46. Kornberg RD, Lorch Y (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98:285–294
47. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837
48. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S et al (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40:897–903
49. Koch F, Andrau JC (2011) Initiating RNA polymerase II and TIPs as hallmarks of enhancer activity and tissue-specificity. Transcription 2:263–268
50. 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
51. Core LJ, Martins AL, Dank CG, Waters CT, Siepel A, Lis JT (2014) Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nat Genet 46:1311–1320
52. Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J (2011) A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470:279–283
53. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ et al (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci USA 107:21931–21936
54. Zentner GE, Tesar PJ, Scacheri PC (2011) Epigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions. Genome Res 21:1273–1283
55. Bogdanovic O, Fernandez-Miñán A, Tena JJ, de la Calle-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 22:2043–2053
56. Bonn S, Zinzen RP, Girardot C, Gustafson EH, Perez-Gonzalez A, Delhomme N et al (2012) Tissue specific analysis of chromatin states identifies temporal signatures of enhancer activity during embryonic development. Nat Genet 44:148–156
57. Whyte WA, Bilodeau S, Orlando DA, Hoke HA, Frampton GM, Foster CT et al (2012) Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. Nature 482:221–225
58. Altaf M, Auger A, Monnet-Saksouk J, Brodeur J, Piquet S, Cramet M et al (2010) NuA4-dependent acetylation of nucleosomal histones H4 and H2A directly stimulates incorporation of H2A.Z by the SWR1 complex. J Biol Chem 285:15966–15977
59. Jeong KW, Kim K, Situ AJ, Ulmer TS, An W, Stallcup MR (2011) Recognition of enhancer element-specific histone methylation by TIP60 in transcriptional activation. Nat Struct Mol Biol 18:1358–1365
60. Lan F, Collins RE, De Cegli R, Alpatov R, Horton JR, Shi X et al (2007) Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression. Nature 488:718–722
61. Ooi SKT, Qiu C, Bernstein E, Li K, Jia D, Yang Z et al (2007) DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448:714–717
62. Lyko F, Ramsahoye BA, Jaenisch R (2000) DNA methylation in Drosophila melanogaster. Nature 408:538–540
63. Cho H, Orphanides G, Sun X, Yang X-J, Ogryzko V, Lees E et al (1998) A human RNA polymerase II complex containing factors that modify chromatin structure. Mol Cell Biol 18:5355–5363
64. Visel A, Blow MJ, Li Z, Zhang T, Akiyama JA, Holt A et al (2009) ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457:854–858
65. Yao TP, Oh SP, Fuchs M, Zhou ND, Ch’ng LE, Newsome D et al (1998) Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93:361–372
66. Tie F, Banerjee R, Stratton CA, Prasad-Sinha J, Stepanik V, Zlobin A et al (2009) CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136:3131–3141
67. Jin Q, Yu LR, Wang L, Zhang Z, Kasper LH, Lee JE et al (2011) Distinct roles of GCN5/PCAF-mediated H3K9ac and CB/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J 30:249–262
68. Holmqvist P-H, Mannervik M (2013) Genomic occupancy of the transcriptional co-activators p300 and CBP. Transcription 4:18–23
69. Mouchiroud L, Eichner LJ, Shaw RJ, Auwerx J (2014) Transcriptional coregulators: fine-tuning metabolism. Cell Metab 20:26–40
70. Cai L, Sutter BM, Li B, Tu BP (2011) Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell 42:426–437
71. Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J et al (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465:182–187
72. Krebs AR, Karmodiya K, Lindahl-Allen M, Struhl K, 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
73. Daitoku H, Sakamaki J, Fukamizu A (2001) Regulation of FoxO transcription factors by acetylation and protein–protein interactions. Biochem Biophys Acta 1813:1954–1960
74. Speranzini V, Pilotto S, Sixma TK, Mattevi A (2016) Touch, act and go: landing and operating on nucleosomes. EMBO J 35:376–388
75. Tie F, Banerjee R, Conrad PA, Scacheri PC, Harte PJ (2012) Histone demethylase UTX and chromatin remodeler BRM bind directly to CBP and modulate acetylation of histone H3 lysine 27. Mol Cell Biol 32:2323–2334
76. Hödl M, Basler K (2012) Transcription in the absence of histone H3.2 and H3K4 methylation. Curr Biol 22:2253–2257
77. Pengelly AR, Copur Ö, Jäckle H, Herzig A, Müller J (2013) A histone mutant reproduces the phenotype caused by loss of histone-modifying factor Polycomb. Science 339:698–699
78. Hathaway NA, Bell O, Hodges C, Miller EL, Neel DS, Crabtree GR (2012) Dynamics and memory of heterochromatin in living cells. Cell 149:1447–1460
79. Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z et al (2008) High-resolution mapping and characterization of open chromatin across the genome. Cell 132:311–322
80. Sabo PJ, Kuehn MS, Thurman R, Johnson BE, Johnson EM, Cao H et al (2006) Genome-scale mapping of DNase I sensitivity in vivo using DNA microarrays. Nat Methods 3:511–518
81. Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E et al (2012) The accessible chromatin landscape of human genome. Nature 489:75–82
82. He HH, Meyer CA, Shin H, Bailey ST, Wei G, Wang Q et al (2010) Nucleosome dynamics define transcriptional enhancers. Nat Genet 42:343–347
83. Mavrich TN, Jiang C, Ioshikhes IP, Li X, Venters BJ, Zanton SJ et al (2008) Nucleosome organization in the Drosophila genome. Nature 453:358–364
84. Iyer V, Struhl K (1995) Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. EMBO J 14:2570–2579
85. Anderson JD, Widom J (2001) Poly (dA-dT) promoter elements increase the equilibrium accessibility of nucleosomal DNA target sites. Mol Cell Biol 21:3830–3839
86. Clapier CR, Cairns BR (2009) The biology of chromatin remodeling complexes. Annu Rev Biochem 78:273–304
87. Shones DE, Cui K, Cuddapah S, Roh TY, Barski A, Wang Z et al (2008) Dynamic regulation of nucleosome positioning in the human genome. Cell 132:887–898
88. Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T (2002) SATB1 targets chromatin remodelling to regulate genes over long distances. Nature 419:641–645
89. Yu Y, Chen Y, Kim B, Wang H, Zhao C, He X et al (2013) Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell 152:248–261
90. Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB et al (2004) Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet 36:955–957
91. Schnetz MP, Handoko L, Akhtar-Zaidi B, Bartels CF, Pereira CF, Fisher AG et al (2010) CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression. PLoS Genet 6:e1001023
92. Escamilla-Del-Arenal M, Recillas-Targa F (2008) GATA-1 modulates the chromatin structure and activity of the chicken α-globin 3′ enhancer. Mol Cell Biol 28:575–586
93. García-González E, Recillas-Targa F (2014) A regulatory element affects the activity and chromatin structure of the chicken α-globin 3′ enhancer. Biochim Biophys Acta 1839:1233–1241
94. Xu Z, Meng X, Cai Y, Koury MJ, Brandt SJ (2006) Recruitment of the SWI/SNF protein Brg1 by a multiprotein complex effects transcriptional repression in murine erythroid progenitors. Biochem J 399:297–304
95. Kim SI, Bresnick EH, Bultman SJ (2009) BRG1 directly regulates nucleosome structure and chromatin looping of the alpha globin locus to activate transcription. Nucleic Acids Res 37:6019–6027
96. Almer A, Rudolph H, Hinnen A, Hörz W (1986) Removal of positioned nucleosomes from the yeast PHO5 promoter upon PHO5 induction release additional upstream activating DNA elements. EMBO J 5:2689–2696
97. Richard-Foy H, Hager GL (1987) Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J 6:2321–2328
98. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257
99. Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S, Regev A et al (2014) DNA methylation dynamics of the human preimplantation embryo. Nature 511:611–615
100. Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Schöler A et al (2011) DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480:490–495
101. Neph S, Vierstra J, Stergachis AB, Reynolds AP, Haugen E, Vernot B et al (2012) An expansive human regulatory lexicon encoded in transcription factor footprints. Nature 489:83–90
102. Bock C, Beerman I, Lien W-H, Smith ZD, Gu H, Boyle P, Gnirke A, Fuchs E, Rossi DJ, Meissner A (2012) DNA methylation dynamics during in vivo differentiation of blood and skin stem cells. Mol Cell 47:633–647
103. Shen L, Wu H, Diep D, Yamaguchi S, D’Alessio AC, Fung HL et al (2013) Genome-wide analysis reveals TET-and TDG-dependent 5-methylcytosine oxidation dynamics. Cell 153:692–706
104. Spruijt CG, Gnerlich F, Smits AH, Pfaffeneder T, Jansen PW, Bauer C et al (2013) Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Cell 152:1146–1159
105. Sérandour AA, Avner S, Percevault F, Demay F, Bizot M, Lucchetti-Miganeh C et al (2011) Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers. Genome Res 21:555–565
106. Stroud H, Feng S, Morey Kinney S, Pradhan S, Jacobsen SE (2011) 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol 12:R54
107. Yu M, Hon GC, Szulwach KE, Song CX, Zhang L, Kim A et al (2012) Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell 149:1368–1380
108. Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, Ko M et al (2011) Genome wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473:394–397
109. Wu H, D’Alessio AC, Ito S, Wang Z, Cui K, Zhao K et al (2011) Genome wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev 25:679–684
110. Frauer C, Hoffmann T, Bultmann S, Casa V, Cardoso MC, Antes I et al (2011) Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain. PLoS One 6:e21306
111. Mellén M, Ayata P, Dewell S, Kriaucionis S, Heintz N (2012) MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 151:1417–1430
112. Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J et al (2013) DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 503:371–376
113. Arab K, Park YT, Lindroth AM, Schäfer A, Oakes C et al (2014) Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol Cell 55:604–614
114. De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK et al (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol 8:e1000384
115. Natoli G, Andrau JC (2012) Noncoding transcription at enhancers: general principles and functional models. Annu Rev Genet 46:1–19
116. Mousavi K, Zare H, Koulnis M, Sartorelli V (2014) The emerging roles of eRNAs in transcriptional regulatory networks. RNA Biol 11:106–110
117. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA 106:11667–11672
118. Ørom UA, 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
119. Heard E, Disteche CM (2006) Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes Dev 20:1848–1867
120. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166
121. Lai F, Orom UA, Cesaroni M, Beringer M, Taatjes DJ, Blobel GA et al (2013) Activating RNAs associate with mediator to enhance chromatin architecture and transcription. Nature 494:497–501
122. Dinger ME, Amaral PP, Mercer TR, Pang KC, Bruce SJ, Gardiner BB et al (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res 18:1433–1445
123. Hah N, Danko CG, Core L, Waterfall JJ, Siepel A, Lis JT et al (2011) A rapid, extensive and transient transcriptional response to estrogen signaling in breast cancer cells. Cell 145:622–634
124. Lam MTY, Cho H, Lesch HP, Gosselin D, Heinz S, Tanaka-Oishi Y et al (2013) Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature 498:511–515
125. Li W, Notani D, Ma Q, Tanasa B, Nunez E, Chen AY et al (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498:516–520
126. Mousavi K, Zare H, Dell’Orso S, Grontved L, Gutierrez-Cruz G, Derfoul A et al (2013) eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. Mol Cell 51:606–617
127. Melo CA, Drost J, Wijchers PJ, van de Werken H, de Wit E, Oude Vrielink JA et al (2013) eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell 49:524–535
128. Lam MTY, Li W, Rosenfeld MG, Glass CK (2014) Enhancer RNAs and regulated transcriptional programs. Trends Biochem Sci 39:170–182
129. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A et al (2012) Landscape of transcription in human cells. Nature 489:101–108
130. Kaikkonen MU, Spann NJ, Heinz S, Romanoski CE, Allison KA, Stender JD et al (2013) Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol Cell 51:310–325
131. Schaukowitch K, Joo JY, Liu X et al (2014) Enhancer RNA facilitates NELF release from immediate early genes. Mol Cell 56:29–41
132. Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J et al (2014) An atlas of active enhancers across human cell types and tissues. Nature 507:455–461
133. Jiang C, Pugh F (2009) Nucleosome positioning and gene regulation: advances through genomics. Nat Rev Genet 10:161–172
134. Jansen A, Verstrepen KJ (2011) Nucleosome positioning in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 75:301–320
135. Huang H, Liu H, Sun X (2013) Nucleosome distribution near the 3′ ends of genes in the human genome. Biosci Biotechnol Biochem 77:2051–2055
136. Duttke SH, Lacadie SA, Ibrahaim MM, Glass CK, Corcoran DL, Benner C, Heinz S, Kadonaga JT, Ohler U (2015) Human promoters are intrinsically directional. Mol Cell 57:674–684
137. Leung D, Jung I, Rajagopal N, Schmitt A, Selvaraj S, Lee AY et al (2015) Integrative analysis of haplotype-resolved epigenomes across human tissues. Nature 518:350–354
138. Kowalczyk MS, Hughes JR, Garrick D, Lynch MD, Sharpe JA, Sloane-Stanley JA et al (2012) Intragenic enhancers act as alternative promoters. Mol Cell 45:447–458
139. Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL et al (2010) Mediator and cohesin connect gene expression and chromatin architecture. Nature 467:430–435
140. Risley MD, Clowes C, Yu M, Mitchell K, Hentges KE (2010) The Mediator complex protein Med31 is required for embryonic growth and cell proliferation during mammalian development. Dev Biol 342:146–156
141. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH et al (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153:307–319
142. Malik S, Roeder RG (2010) The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nat Rev Genet 11:761–772
143. Ito T, Ikehara T, Nakagawa T, Kraus WL, Muramatsu M (2000) p300-mediated acetylation facilitates the transfer of histone H2A–H2B dimers from nucleosomes to a histone chaperone. Genes Dev 14:1899–1907
144. Pott S, Lieb JD (2015) What are super-enhancers? Nat Genet 47:8–12
145. Allen BL, Taatjes DJ (2015) The Mediator complex: a central integrator of transcription. Nat Rev Mol Cell Biol 16:155–166
146. Fiering S, Whitelaw E, Martin DI (2000) To be or not to be active: the stochastic nature of enhancer action. BioEssays 4:381–387
147. Plank JL, Dean A (2014) Enhancer function: mechanistic and genome-wide insights come together. Mol Cell 55:5–14
148. Heinz S, Romanoski CE, Benner C, Glass CK (2015) The selection and function of cell type-specific enhancers. Nat Rev Mol Cell Biol 16:144–154
149. Dixon JR, 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
150. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, Servant N et al (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–385
151. Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, Hoichman M et al (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148:458–472
152. Bouwman BA, de Laat W (2015) Getting the genome in shape: the formation of loops, domain and compartments. Genome Biol 16:154
153. Kvon EZ, Kazmar T, Stampfel G, Yáñez-Cuna JO, Pagani M, Schernhuber K et al (2014) Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature 512:91–95
154. Mifsud B, Tavares-Cadete F, Young AN, Sugar R, Schoenfelder S, Ferreira L et al (2015) Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat Genet 47:598–606
155. Jin F, Li Y, Dixon JR, Selvaraj S, Ye Z, Lee AY et al (2013) A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 503:290–294
156. Schoenfelder S, Furlan-Magaril M, Mifsud B, Tavares-Cadete F, Sugar R, Javierre BM et al (2015) The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements. Genome Res 25:582–597
157. Ghavi-Helm Y, Klein FA, Pakodzi T, Ciglar L, Noordermeer D, Huber W et al (2014) Enhancer loops appear stable during development and are associated with paused polymerase. Nature 512:96–100
158. Guo Y, Xu Q, Canzio D, Shou J, Li J, Gorkin DU et al (2015) CRISPR inversion of CTCF sites alters genome topology an enhancer/promoter function. Cell 162:900–910
159. Lupiáñez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E et al (2015) Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161:1012–1025
160. Sanyal A, Lajoie BR, Jain G, Dekker J (2012) The long-range interaction landscape of gene promoters. Nature 489:109–113