155338 20210720115131.0 10.1038/nature12787 doi pmid:24670763 pmid pmc:PMC5215096 pmc 0028-0836 ISSN 1476-4687 ISSN DZNE-2021-00605 English 500 Andersson, Robin 0 An atlas of active enhancers across human cell types and tissues. London [u.a.] 2014 Nature Publ. Group article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1626774577_22306 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation. Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de RNA, Messenger NLM Chemicals Atlases as Topic MeSH Cell Line MeSH Cells, Cultured MeSH Cluster Analysis MeSH Enhancer Elements, Genetic: genetics MeSH Gene Expression Regulation: genetics MeSH Genetic Predisposition to Disease: genetics MeSH HeLa Cells MeSH Humans MeSH Molecular Sequence Annotation MeSH Organ Specificity MeSH Polymorphism, Single Nucleotide: genetics MeSH Promoter Regions, Genetic: genetics MeSH RNA, Messenger: biosynthesis MeSH RNA, Messenger: genetics MeSH Transcription Initiation Site MeSH Transcription Initiation, Genetic MeSH Gebhard, Claudia 1 Miguel-Escalada, Irene 2 Hoof, Ilka 3 Bornholdt, Jette 4 Boyd, Mette 5 Chen, Yun 6 Zhao, Xiaobei 7 Schmidl, Christian 8 Suzuki, Takahiro 9 Ntini, Evgenia 10 Arner, Erik 11 Valen, Eivind 12 Li, Kang 13 Schwarzfischer, Lucia 14 Glatz, Dagmar 15 Raithel, Johanna 16 Lilje, Berit 17 Rapin, Nicolas 18 Bagger, Frederik Otzen 19 Jørgensen, Mette 20 Andersen, Peter Refsing 21 Bertin, Nicolas 22 Rackham, Owen 23 Burroughs, A Maxwell 24 Baillie, J Kenneth 25 Ishizu, Yuri 26 Shimizu, Yuri 27 Furuhata, Erina 28 Maeda, Shiori 29 Negishi, Yutaka 30 Mungall, Christopher J 31 Meehan, Terrence F 32 Lassmann, Timo 33 Itoh, Masayoshi 34 Kawaji, Hideya 35 Kondo, Naoto 36 Kawai, Jun 37 Lennartsson, Andreas 38 Daub, Carsten O 39 Heutink, Peter P:(DE-2719)2810728 40 dzne Hume, David A 41 Jensen, Torben Heick 42 Suzuki, Harukazu 43 Hayashizaki, Yoshihide 44 Müller, Ferenc 45 Forrest, Alistair R R 46 Carninci, Piero 47 Rehli, Michael 48 Sandelin, Albin 49 Forrest, Alistair R R 50 Kawaji, Hideya 51 Rehli, Michael 52 Baillie, J Kenneth 53 de Hoon, Michiel J L 54 Haberle, Vanja 55 Lassmann, Timo 56 Kulakovskiy, Ivan V 57 Lizio, Marina 58 Itoh, Masayoshi 59 Andersson, Robin 60 Mungall, Christoher J 61 Meehan, Terrence F 62 Schmeier, Sebastian 63 Bertin, Nicolas 64 Jørgensen, Mette 65 Dimont, Emmanuel 66 Arner, Erik 67 Schmid, Christian 68 Schaefer, Ulf 69 Medvedeva, Yulia A 70 Plessy, Charles 71 Vitezic, Morana 72 Severin, James 73 Semple, Colin A 74 Ishizu, Yuri 75 Young, Robert S 76 Francescatto, Margherita P:(DE-2719)2810784 77 dzne Alam, Intikhab 78 Albanese, Davide 79 Altschuler, Gabriel M 80 Arakawa, Takahiro 81 Archer, John A C 82 Arner, Peter 83 Babina, Magda 84 Rennie, Sarah 85 Balwierz, Piotr J 86 Beckhouse, Anthony G 87 Pradhan-Bhatt, Swati 88 Blake, Judith A 89 Blumenthal, Antje 90 Bodega, Beatrice 91 Bonetti, Alessandro 92 Briggs, James 93 Brombacher, Frank 94 Burroughs, A Maxwell 95 Califano, Andrea 96 Cannistracti, Carlo V 97 Carbajo, Daniel 98 Chen, Yun 99 Chierici, Marco 100 Ciani, Yari 101 Clevers, Hans C 102 Dalla, Emiliano 103 Davis, Carrie A 104 Detmar, Michael 105 Diehl, Alexander D 106 Dohi, Taeko 107 Drabløs, Finn 108 Edge, Albert S B 109 Edinger, Matthias 110 Ekwall, Karl 111 Endoh, Mitsuhiro 112 Enomoto, Hideki 113 Fagiolini, Michela 114 Fairbairn, Lynsey 115 Fang, Hai 116 Farach-Carson, Mary C 117 Faulkner, Geoffrey J 118 Favorov, Alexander V 119 Fisher, Malcolm E 120 Frith, Martin C 121 Fujita, Rie 122 Fukuda, Shiro 123 Furlanello, Cesare 124 Furuno, Masaaki 125 Furusawa, Jun-ichi 126 Geijtenbeek, Teunis B 127 Gibson, Andrew P 128 Gingeras, Thomas 129 Goldowitz, Daniel 130 Gough, Julian 131 Guhl, Sven 132 Guler, Reto 133 Gustincich, Stefano 134 Ha, Thomas J 135 Hamaguchi, Masahide 136 Hara, Mitsuko 137 Harbers, Matthias 138 Harshbarger, Jayson 139 Hasegawa, Akira 140 Hasegawa, Yuki 141 Hashimoto, Takehiro 142 Herlyn, Meenhard 143 Hitchens, Kelly J 144 Ho Sui, Shannan J 145 Hofman, Oliver M 146 Hoof, Ilka 147 Hori, Fumi 148 Huminiecki, Lukasz 149 Iida, Kei 150 Ikawa, Tomokatsu 151 Jankovic, Boris R 152 Jia, Hui 153 Joshi, Anagha 154 Jurman, Giuseppe 155 Kaczkowski, Bogumil 156 Kai, Chieko 157 Kaida, Kaoru 158 Kaiho, Ai 159 Kajiyama, Kazuhiro 160 Kanamori-Katayama, Mutsumi 161 Kasianov, Artem S 162 Kasukawa, Takeya 163 Katayama, Shintaro 164 Kato, Sachi 165 Kawaguchi, Shuji 166 Kawamoto, Hiroshi 167 Kawamura, Yuki I 168 Kawashima, Tsugumi 169 Kempfle, Judith S 170 Kenna, Tony J 171 Kere, Juha 172 Khachigian, Levon M 173 Kitamura, Toshio 174 Klinken, S Peter 175 Knox, Alan J 176 Kojima, Miki 177 Kojima, Soichi 178 Kondo, Naoto 179 Koseki, Haruhiko 180 Koyasu, Shigeo 181 Krampitz, Sarah 182 Kubosaki, Atsutaka 183 Kwon, Andrew T 184 Laros, Jeroen F J 185 Lee, Weonju 186 Lennartsson, Andreas 187 Li, Kang 188 Lilje, Berit 189 Lipovich, Leonard 190 Mackay-Sim, Alan 191 Manabe, Ri-ichiroh 192 Mar, Jessica C 193 Marchand, Benoit 194 Mathelier, Anthony 195 Mejhert, Niklas 196 Meynert, Alison 197 Mizuno, Yosuke 198 de Lima Morais, David A 199 Morikawa, Hiromasa 200 Morimoto, Mitsuru 201 Moro, Kazuyo 202 Motakis, Efthymios 203 Motohashi, Hozumi 204 Mummery, Christine L 205 Murata, Mitsuyoshi 206 Nagao-Sato, Sayaka 207 Nakachi, Yutaka 208 Nakahara, Fumio 209 Nakamura, Toshiyuki 210 Nakamura, Yukio 211 Nakazato, Kenichi 212 van Nimwegen, Erik 213 Ninomiya, Noriko 214 Nishiyori, Hiromi 215 Noma, Shohei 216 Nozaki, Tadasuke 217 Ogishima, Soichi 218 Ohkura, Naganari 219 Ohmiya, Hiroko 220 Ohno, Hiroshi 221 Onshima, Mitsuhiro 222 Okada-Hatakeyama, Mariko 223 Okazaki, Yasushi 224 Orlando, Valerie 225 Ovchinnikov, Dmitry A 226 Pain, Arnab 227 Passier, Robert 228 Patrikakis, Margaret 229 Persson, Helena 230 Piazza, Silvano 231 Prendergast, James G D 232 Rackham, Owen J L 233 Ramilowski, Jordan A 234 Rashid, Mamoon 235 Ravasi, Timothy 236 Rizzu, Patrizia P:(DE-2719)2810718 237 dzne Roncador, Marco 238 Roy, Sugata 239 Rye, Morten B 240 Saijyo, Eri 241 Sajantila, Antti 242 Saka, Akiko 243 Sakaguchi, Shimon 244 Sakai, Mizuho 245 Sato, Hiroki 246 Satoh, Hironori 247 Savvi, Suzana 248 Saxena, Alka 249 Schneider, Claudio 250 Schultes, Erik A 251 Schultz-Tanzil, Gudula G 252 Schwegmann, Anita 253 Sengstag, Thierry 254 Sheng, Guojun 255 Shimoji, Hisashi 256 Shimoni, Yishai 257 Shin, Jay W 258 Simon, Christophe 259 Sugiyama, Daisuke 260 Sugiyama, Takaaki 261 Suzuki, Masanori 262 Suzuki, Naoko 263 Swoboda, Rolf K 264 't Hoen, Peter A C 265 Tagami, Michihira 266 Takahashi, Naoko 267 Takai, Jun 268 Tanaka, Hiroshi 269 Tatsukawa, Hideki 270 Tatum, Zuotian 271 Thompson, Mark 272 Toyoda, Hiroo 273 Toyodo, Tetsuro 274 Valen, Eivind 275 van de Wetering, Marc 276 van den Berg, Linda M 277 Verardo, Roberto 278 Vijayan, Dipti 279 Vorontsov, Ilya E 280 Wasserman, Wyeth W 281 Watanabe, Shoko 282 Wells, Christine A 283 Winteringham, Louise N 284 Wolvetang, Ernst 285 Wood, Emily J 286 Yamaguchi, Yoko 287 Yamamoto, Masayuki 288 Yoneda, Misako 289 Yonekura, Yohei 290 Yoshida, Shigehiro 291 Zabierowski, Susan E 292 Zhang, Peter G 293 Zhao, Xiaobei 294 Zucchelli, Silvia 295 Summers, Kim M 296 Suzuki, Harukazu 297 Daub, Carsten O 298 Kawai, Jun 299 Heutink, Peter P:(DE-2719)2810728 300 dzne Hide, Winston 301 Freeman, Tom C 302 Lenhard, Boris 303 Bajic, Vladimir B 304 Taylor, Martin S 305 Makeev, Vsevolod J 306 Sandelin, Allbin 307 Hume, David A 308 Carninci, Piero 309 Hayashizaki, Yoshihide 310 10.1038/nature12787 Vol. 507, no. 7493, p. 455 - 461 PERI:(DE-600)1413423-8 7493 455 - 461 Nature <London> 507 2014 1476-4687 External Institute I:(DE-HGF)0 Extern 40 P:(DE-2719)2810728 External Institute I:(DE-HGF)0 Extern 77 P:(DE-2719)2810784 External Institute I:(DE-HGF)0 Extern 237 P:(DE-2719)2810718 External Institute I:(DE-HGF)0 Extern 300 P:(DE-2719)2810728 Nationallizenz StatID:(DE-HGF)0420 StatID 2021-01-27 ger JCR StatID:(DE-HGF)0100 StatID NATURE : 2019 2021-01-27 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2021-01-27 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2021-01-27 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2021-01-27 Peer Review StatID:(DE-HGF)0030 StatID ASC 2021-01-27 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2021-01-27 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2021-01-27 DBCoverage StatID:(DE-HGF)1200 StatID Chemical Reactions 2021-01-27 DBCoverage 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