Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

被引：415

作者：

Arner, Erik ^{[1
,2
,12
,13
]}

Daub, Carsten O. ^{[1
,2
]}

Vitting-Seerup, Kristoffer ^{[39
]}

Andersson, Robin ^{[39
]}

Lilje, Berit ^{[39
]}

Drablos, Finn ^{[34
]}

Lennartsson, Andreas ^{[14
]}

Roennerblad, Michelle ^{[14
]}

Hrydziuszko, Olga ^{[12
,13
]}

Vitezic, Morana ^{[39
]}

Freeman, Tom C. ^{[40
]}

Alhendi, Ahmad M. N. ^{[10
]}

Arner, Peter ^{[17
,18
]}

Axton, Richard ^{[40
]}

Baillie, J. Kenneth ^{[40
]}

Beckhouse, Anthony ^{[5
]}

Bodega, Beatrice ^{[30
]}

Briggs, James ^{[5
]}

Brombacher, Frank ^{[22
,23
]}

Davis, Margaret ^{[40
]}

Detmar, Michael ^{[29
]}

Ehrlund, Anna ^{[17
,18
]}

Endoh, Mitsuhiro ^{[6
,36
,37
]}

Eslami, Afsaneh ^{[11
]}

Fagiolini, Michela ^{[24
]}

Fairbairn, Lynsey ^{[40
]}

Faulkner, Geoffrey J. ^{[8
]}

Ferrai, Carmelo ^{[6
]}

Fisher, Malcolm E. ^{[40
]}

Forrester, Lesley ^{[40
]}

Goldowitz, Daniel ^{[16
]}

Guler, Reto ^{[22
,23
]}

Ha, Thomas ^{[16
]}

Hara, Mitsuko ^{[38
]}

Herlyn, Meenhard ^{[32
]}

Ikawa, Tomokatsu ^{[36
,37
]}

Kai, Chieko ^{[31
]}

Kawamoto, Hiroshi ^{[36
]}

Khachigian, Levon M. ^{[10
]}

Klinken, S. Peter ^{[26
,27
]}

Kojima, Soichi ^{[38
]}

Koseki, Haruhiko ^{[36
,37
]}

Klein, Sarah

Mejhert, Niklas ^{[17
,18
]}

Miyaguchi, Ken ^{[11
]}

Mizuno, Yosuke ^{[20
]}

Morimoto, Mitsuru ^{[35
]}

Morris, Kelly J. ^{[6
]}

Mummery, Christine ^{[4
]}

Nakachi, Yutaka ^{[20
,21
]}

机构：

[1] RIKEN Omics Sci Ctr OSC, Tsurumi Ku, 1-7-22 Suehiro cho, Yokohama, Kanagawa 2300045, Japan

[2] RIKEN Ctr Life Sci Technol, Div Genom Technol CLST DGT, Tsurumi Ku, 1-7-22 Suehiro cho, Yokohama, Kanagawa 2300045, Japan

[3] RIKEN Prevent Med & Diag Innovat Program PMI, 2-1 Hirosawa,Wako-shi, Saitama 3510198, Japan

[4] Leiden Univ Med Ctr, Anat & Embryol, Einthovenweg 20,POB 9600, NL-2300 RC Leiden, Netherlands

[5] Univ Queensland, AIBN, Brisbane, Qld 4072, Australia

[6] Berlin Inst Med Syst Biol, Max Delbrueck Ctr, Robert Roessle Str 10, D-13125 Berlin, Germany

[7] King Abdullah Univ Sci & Technol KAUST, Biol & Environm Sci & Engn Div, Ibn Al Haytham Bldg-2, Thuwal, Saudi Arabia

[8] Mater Med Res Inst, Canc Biol Program, Raymond Terrace, South Brisbane, Qld 4101, Australia

[9] Kyushu Univ Hosp, Ctr Clin & Translat Reseach, 3-1-1 Maidashi, Higashi Ku, Fukuoka 8128582, Japan

[10] Univ New South Wales, Ctr Vasc Res, Sydney, NSW, Australia

[11] Tokyo Med & Dent Univ, Med Res Inst, Dept Bioinformat, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan

[12] Karolinska Inst, Dept Biosciences & Nutr, SE-14186 Stockholm, Sweden

[13] Karolinska Inst, Sci Life Lab, SE-14186 Stockholm, Sweden

[14] Karolinska Inst, Dept Biosciences & Nutr, Ctr Biosciences, Halsovagen 7-9, SE-14183 Huddinge, Sweden

[15] Kyushu Univ, Dept Clin Study, Ctr Adv Med Innovat, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[16] Univ British Columbia, Child & Family Res Inst, Dept Med Genet, Ctr Mol Med & Therapeut, 950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada

[17] Karolinska Inst, Dept Med, S-14186 Stockholm, Sweden

[18] Karolinska Univ Hosp, Ctr Metab & Endocrinol, S-14186 Stockholm, Sweden

[19] Univ Buffalo, Sch Med & Biomed Sci, Dept Neurol, New York State Ctr Excellence Bioinformat & Life, 701 Ellicott St, Buffalo, NY 14203 USA

[20] Saitama Med Univ, Div Funct Genom & Syst Med, Res Ctr Genom Med, 1397-1 Yamane, Hidaka, Saitama 3501241, Japan

[21] Saitama Med Univ, Div Translat Res, Res Ctr Genom Med, 1397-1 Yamane, Hidaka, Saitama 3501241, Japan

[22] Int Ctr Genet Engn Biotechnol ICGEB Cape Town com, Immunol & Infect Dis, Anzio Rd, Cape Town, South Africa

[23] Univ Cape Town, Inst Infect Dis & Mol Med IDM, Div Immunol, Anzio Rd, Cape Town, South Africa

[24] Harvard Med Sch, Childrens Hosp, F M Kirby Neurobiol Ctr, 300 Longwood Ave, Boston, MA 02115 USA

[25] Lawrence Berkeley Natl Lab, Genom Div, 1 Cyclotron Rd, Berkeley, CA 94720 USA

[26] Univ Western Australia, Harry Perkins Inst Med Res, Nedlands, WA, Australia

[27] Univ Western Australia, Ctr Med Res Ctr, QEII Med Ctr, QQ Block, Nedlands, WA, Australia

[28] Univ Glasgow, Inst Infect Immun & Inflammat, MVLS, Glasgow, Lanark, Scotland

[29] Inst Pharmaceut Sci, ETH Zurich, Vladimir Prelog Weg 3, CH-8093 Zurich, Switzerland

[30] IRCCS Fnd Santa Lucia, Via Fosso Fiorano 64, I-00143 Rome, Italy

[31] Univ Tokyo, Inst Med Sci, Lab Anim Res Ctr, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan

[32] Wistar Inst Anat & Biol, Melanoma Res Ctr, 3601 Spruce St, Philadelphia, PA 19104 USA

[33] European Mol Biol Lab European Bioinformat Inst, Mouse Informat, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England

[34] Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Fac Med, POB 8905, NO-7491 Trondheim, Norway

[35] RIKEN Ctr Dev Biol CDB, Chuo Ku, 2-2-3 Minatojimaminamimachi, Kobe, Hyogo 6500047, Japan

[36] RIKEN Res Ctr Allergy & Immunol RCAI, Tsurumi Ku, 1-7-22 Suehirocho, Yokohama, Kanagawa 2300045, Japan

[37] RIKEN Ctr Integrat Med Sci, 1-7-22 Suehiro cho, Yokohama, Kanagawa 2300045, Japan

[38] RIKEN Ctr Life Sci Technol, Div Bio Funct Dynam Imaging CLST DBDI, 2-1 Hirosawa, Wako, Saitama 3510198, Japan

[39] Univ Copenhagen, Dept Biol & Biotech Res & Innovat Ctr BRIC, Bioinformat Ctr, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark

[40] Univ Edinburgh, Roslin Inst & Royal Dick Sch Vet Studies, Easter Bush, Edinburgh EH25 9RG, Midlothian, Scotland

[41] Natl Univ Singapore, Canc Sci Inst Singapore, Ctr Translat Med, 14 Med Dr, Singapore 1201, Singapore

[42] Tohoku Univ, Dept Bioclin Informat, Tohoku Med Megabank Org, Aoba Ku, Seiryo cho 2-1, Sendai shi, Miyagi 9808573, Japan

来源：

SCIENCE | 2015年 / 347卷 / 6225期

基金：

英国生物技术与生命科学研究理事会;

关键词：

RNAS;

D O I：

10.1126/science.1259418

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.

引用

页码：1010 / 1014

页数：5

共 20 条

[1] Nuclear stability and transcriptional directionality separate functionally distinct RNA species [J].

Andersson, Robin ;

Andersen, Peter Refsing ;

Valen, Eivind ;

Core, Leighton J. ;

Bornholdt, Jette ;

Boyd, Mette ;

Jensen, Torben Heick ;

Sandelin, Albin .

NATURE COMMUNICATIONS, 2014, 5

[2] An atlas of active enhancers across human cell types and tissues [J].

Andersson, Robin ;

Gebhard, Claudia ;

Miguel-Escalada, Irene ;

Hoof, Ilka ;

Bornholdt, Jette ;

Boyd, Mette ;

Chen, Yun ;

Zhao, Xiaobei ;

Schmidl, Christian ;

Suzuki, Takahiro ;

Ntini, Evgenia ;

Arner, Erik ;

Valen, Eivind ;

Li, Kang ;

Schwarzfischer, Lucia ;

Glatz, Dagmar ;

Raithel, Johanna ;

Lilje, Berit ;

Rapin, Nicolas ;

Bagger, Frederik Otzen ;

Jorgensen, Mette ;

Andersen, Peter Refsing ;

Bertin, Nicolas ;

Rackham, Owen ;

Burroughs, A. Maxwell ;

Baillie, J. Kenneth ;

Ishizu, Yuri ;

Shimizu, Yuri ;

Furuhata, Erina ;

Maeda, Shiori ;

Negishi, Yutaka ;

Mungall, Christopher J. ;

Meehan, Terrence F. ;

Lassmann, Timo ;

Itoh, Masayoshi ;

Kawaji, Hideya ;

Kondo, Naoto ;

Kawai, Jun ;

Lennartsson, Andreas ;

Daub, Carsten O. ;

Heutink, Peter ;

Hume, David A. ;

Jensen, Torben Heick ;

Suzuki, Harukazu ;

Hayashizaki, Yoshihide ;

Mueller, Ferenc ;

Forrest, Alistair R. R. ;

Carninci, Piero ;

Rehli, Michael ;

Sandelin, Albin .

NATURE, 2014, 507 (7493) :455-+

[3] Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development [J].

Bonn, Stefan ;

Zinzen, Robert P. ;

Girardot, Charles ;

Gustafson, E. Hilary ;

Perez-Gonzalez, Alexis ;

Delhomme, Nicolas ;

Ghavi-Helm, Yad ;

Wilczynski, Bartek ;

Riddell, Andrew ;

Furlong, Eileen E. M. .

NATURE GENETICS, 2012, 44 (02) :148-156

[4] Topological domains in mammalian genomes identified by analysis of chromatin interactions [J].

Dixon, Jesse R. ;

Selvaraj, Siddarth ;

Yue, Feng ;

Kim, Audrey ;

Li, Yan ;

Shen, Yin ;

Hu, Ming ;

Liu, Jun S. ;

Ren, Bing .

NATURE, 2012, 485 (7398) :376-380

[5] An integrated encyclopedia of DNA elements in the human genome [J].

Dunham, Ian ;

Kundaje, Anshul ;

Aldred, Shelley F. ;

Collins, Patrick J. ;

Davis, CarrieA. ;

Doyle, Francis ;

Epstein, Charles B. ;

Frietze, Seth ;

Harrow, Jennifer ;

Kaul, Rajinder ;

Khatun, Jainab ;

Lajoie, Bryan R. ;

Landt, Stephen G. ;

Lee, Bum-Kyu ;

Pauli, Florencia ;

Rosenbloom, Kate R. ;

Sabo, Peter ;

Safi, Alexias ;

Sanyal, Amartya ;

Shoresh, Noam ;

Simon, Jeremy M. ;

Song, Lingyun ;

Trinklein, Nathan D. ;

Altshuler, Robert C. ;

Birney, Ewan ;

Brown, James B. ;

Cheng, Chao ;

Djebali, Sarah ;

Dong, Xianjun ;

Dunham, Ian ;

Ernst, Jason ;

Furey, Terrence S. ;

Gerstein, Mark ;

Giardine, Belinda ;

Greven, Melissa ;

Hardison, Ross C. ;

Harris, Robert S. ;

Herrero, Javier ;

Hoffman, Michael M. ;

Iyer, Sowmya ;

Kellis, Manolis ;

Khatun, Jainab ;

Kheradpour, Pouya ;

Kundaje, Anshul ;

Lassmann, Timo ;

Li, Qunhua ;

Lin, Xinying ;

Marinov, Georgi K. ;

Merkel, Angelika ;

Mortazavi, Ali .

NATURE, 2012, 489 (7414) :57-74

[6] A promoter-level mammalian expression atlas [J].

Forrest, Alistair R. R. ;

Kawaji, Hideya ;

Rehli, Michael ;

Baillie, J. Kenneth ;

de Hoon, Michiel J. L. ;

Haberle, Vanja ;

Lassmann, Timo ;

Kulakovskiy, Ivan V. ;

Lizio, Marina ;

Itoh, Masayoshi ;

Andersson, Robin ;

Mungall, Christopher J. ;

Meehan, Terrence F. ;

Schmeier, Sebastian ;

Bertin, Nicolas ;

Jorgensen, Mette ;

Dimont, Emmanuel ;

Arner, Erik ;

Schmidl, Christian ;

Schaefer, Ulf ;

Medvedeva, Yulia A. ;

Plessy, Charles ;

Vitezic, Morana ;

Severin, Jessica ;

Semple, Colin A. ;

Ishizu, Yuri ;

Young, Robert S. ;

Francescatto, Margherita ;

Alam, Intikhab ;

Albanese, Davide ;

Altschuler, Gabriel M. ;

Arakawa, Takahiro ;

Archer, John A. C. ;

Arner, Peter ;

Babina, Magda ;

Rennie, Sarah ;

Balwierz, Piotr J. ;

Beckhouse, Anthony G. ;

Pradhan-Bhatt, Swati ;

Blake, Judith A. ;

Blumenthal, Antje ;

Bodega, Beatrice ;

Bonetti, Alessandro ;

Briggs, James ;

Brombacher, Frank ;

Burroughs, A. Maxwell ;

Califano, Andrea ;

Cannistraci, Carlo V. ;

Carbajo, Daniel ;

Chen, Yun .

NATURE, 2014, 507 (7493) :462-+

[7] Enhancer transcripts mark active estrogen receptor binding sites [J].

Hah, Nasun ;

Murakami, Shino ;

Nagari, Anusha ;

Danko, Charles G. ;

Kraus, W. Lee .

GENOME RESEARCH, 2013, 23 (08) :1210-1223

[8] Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation [J].

Hsieh, Chen-Lin ;

Fei, Teng ;

Chen, Yiwen ;

Li, Tiantian ;

Gao, Yanfei ;

Wang, Xiaodong ;

Sun, Tong ;

Sweeney, Christopher J. ;

Lee, Gwo-Shu Mary ;

Chen, Shaoyong ;

Balk, Steven P. ;

Liu, Xiaole Shirley ;

Brown, Myles ;

Kantoff, Philip W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (20) :7319-7324

[9] Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes [J].

Iiott, Nicholas E. ;

Heward, James A. ;

Roux, Benoit ;

Tsitsiou, Eleni ;

Fenwick, Peter S. ;

Lenzi, Luca ;

Goodhead, Ian ;

Hertz-Fowler, Christiane ;

Heger, Andreas ;

Hall, Neil ;

Donnelly, Louise E. ;

Sims, David ;

Lindsay, Mark A. .

NATURE COMMUNICATIONS, 2014, 5

[10] Remodeling of the Enhancer Landscape during Macrophage Activation Is Coupled to Enhancer Transcription [J].

Kaikkonen, Minna U. ;

Spann, Nathanael J. ;

Heinz, Sven ;

Romanoski, Casey E. ;

Allison, Karmel A. ;

Stender, Joshua D. ;

Chun, Hyun B. ;

Tough, David F. ;

Prinjha, Rab K. ;

Benner, Christopher ;

Glass, Christopher K. .

MOLECULAR CELL, 2013, 51 (03) :310-325

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