Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Erik Arner; Carsten O. Daub; Kristoffer Vitting-Seerup; Robin Andersson; Berit Lilje; Finn Drabløs; Andreas Lennartsson; Michelle Rönnerblad; Olga Hrydziuszko; Morana Vitezic; Tom C Freeman; Ahmad M N Alhendi; Peter Arner; Richard Axton; J Kenneth Baillie; Anthony Beckhouse; Beatrice Bodega; James Briggs; Frank Brombacher; Margaret Davis; Michael Detmar; Anna Ehrlund; Mitsuhiro Endoh; Afsaneh Eslami; Michela Fagiolini; Lynsey Fairbairn; Geoffrey J Faulkner; Carmelo Ferrai; Malcolm E Fisher; Lesley Forrester; Daniel Goldowitz; Reto Guler; Thomas Ha; Mitsuko Hara; Meenhard Herlyn; Tomokatsu Ikawa; Chieko Kai; Hiroshi Kawamoto; Levon M Khachigian; S Peter Klinken; Soichi Kojima; Haruhiko Koseki; Sarah Klein; Niklas Mejhert; Ken Miyaguchi; Yosuke Mizuno; Mitsuru Morimoto; Kelly J Morris; Christine Mummery; Yutaka Nakachi; Soichi Ogishima; Mariko Okada-Hatakeyama; Yasushi Okazaki; Valerio Orlando; Dmitry Ovchinnikov; Robert Passier; Margaret Patrikakis; Ana Pombo; Xian-Yang Qin; Sugata Roy; Hiroki Sato; Suzana Savvi; Alka Saxena; Anita Schwegmann; Daisuke Sugiyama; Rolf Swoboda; Hiroshi Tanaka; Andru Tomoiu; Louise N Winteringham; Ernst Wolvetang; Chiyo Yanagi-Mizuochi; Misako Yoneda; Susan Zabierowski; Peter Zhang; Imad Abugessaisa; Nicolas Bertin; Alexander D Diehl; Shiro Fukuda; Masaaki Furuno; Jayson Harshbarger; Akira Hasegawa; Fumi Hori; Sachi Ishikawa-Kato; Yuri Ishizu; Masayoshi Itoh; Tsugumi Kawashima; Miki Kojima; Naoto Kondo; Marina Lizio; Terrence F Meehan; Christopher J Mungall; Mitsuyoshi Murata; Hiromi Nishiyori-Sueki; Serkan Sahin; Sayaka Nagao-Sato; Jessica Severin; Michiel J L de Hoon; Jun Kawai; Takeya Kasukawa; Timo Lassmann; Harukazu Suzuki; Hideya Kawaji; Kim M Summers; Christine Wells; David A Hume; Alistair R R Forrest; Albin Gustav Sandelin; Piero Carninci; Yoshihide Hayashizaki

doi:10.1126/science.1259418

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Erik Arner, Carsten O. Daub, Kristoffer Vitting-Seerup, Robin Andersson, Berit Lilje, Finn Drabløs, Andreas Lennartsson, Michelle Rönnerblad, Olga Hrydziuszko, Morana Vitezic, Tom C Freeman, Ahmad M N Alhendi, Peter Arner, Richard Axton, J Kenneth Baillie, Anthony Beckhouse, Beatrice Bodega, James Briggs, Frank Brombacher, Margaret DavisMichael Detmar, Anna Ehrlund, Mitsuhiro Endoh, Afsaneh Eslami, Michela Fagiolini, Lynsey Fairbairn, Geoffrey J Faulkner, Carmelo Ferrai, Malcolm E Fisher, Lesley Forrester, Daniel Goldowitz, Reto Guler, Thomas Ha, Mitsuko Hara, Meenhard Herlyn, Tomokatsu Ikawa, Chieko Kai, Hiroshi Kawamoto, Levon M Khachigian, S Peter Klinken, Soichi Kojima, Haruhiko Koseki, Sarah Klein, Niklas Mejhert, Ken Miyaguchi, Yosuke Mizuno, Mitsuru Morimoto, Kelly J Morris, Christine Mummery, Yutaka Nakachi, Soichi Ogishima, Mariko Okada-Hatakeyama, Yasushi Okazaki, Valerio Orlando, Dmitry Ovchinnikov, Robert Passier, Margaret Patrikakis, Ana Pombo, Xian-Yang Qin, Sugata Roy, Hiroki Sato, Suzana Savvi, Alka Saxena, Anita Schwegmann, Daisuke Sugiyama, Rolf Swoboda, Hiroshi Tanaka, Andru Tomoiu, Louise N Winteringham, Ernst Wolvetang, Chiyo Yanagi-Mizuochi, Misako Yoneda, Susan Zabierowski, Peter Zhang, Imad Abugessaisa, Nicolas Bertin, Alexander D Diehl, Shiro Fukuda, Masaaki Furuno, Jayson Harshbarger, Akira Hasegawa, Fumi Hori, Sachi Ishikawa-Kato, Yuri Ishizu, Masayoshi Itoh, Tsugumi Kawashima, Miki Kojima, Naoto Kondo, Marina Lizio, Terrence F Meehan, Christopher J Mungall, Mitsuyoshi Murata, Hiromi Nishiyori-Sueki, Serkan Sahin, Sayaka Nagao-Sato, Jessica Severin, Michiel J L de Hoon, Jun Kawai, Takeya Kasukawa, Timo Lassmann, Harukazu Suzuki, Hideya Kawaji, Kim M Summers, Christine Wells, David A Hume, Alistair R R Forrest, Albin Gustav Sandelin, Piero Carninci, Yoshihide Hayashizaki

Computational and RNA Biology

299 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Science (New York, N.Y.)
Volume	347
Issue number	6225
Pages (from-to)	1010-1014
Number of pages	5
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1259418
Publication status	Published - 27 Feb 2015

Access to Document

10.1126/science.1259418

https://www.science.org/cms/asset/3d97122b-b33e-4de2-931c-c05b269f4b76/pap.pdf

Cite this

Arner, E., Daub, C. O., Vitting-Seerup, K., Andersson, R., Lilje, B., Drabløs, F., Lennartsson, A., Rönnerblad, M., Hrydziuszko, O., Vitezic, M., Freeman, T. C., Alhendi, A. M. N., Arner, P., Axton, R., Baillie, J. K., Beckhouse, A., Bodega, B., Briggs, J., Brombacher, F., ... Hayashizaki, Y. (2015). Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science (New York, N.Y.), 347(6225), 1010-1014. https://doi.org/10.1126/science.1259418

Arner, E, Daub, CO, Vitting-Seerup, K, Andersson, R, Lilje, B, Drabløs, F, Lennartsson, A, Rönnerblad, M, Hrydziuszko, O, Vitezic, M, Freeman, TC, Alhendi, AMN, Arner, P, Axton, R, Baillie, JK, Beckhouse, A, Bodega, B, Briggs, J, Brombacher, F, Davis, M, Detmar, M, Ehrlund, A, Endoh, M, Eslami, A, Fagiolini, M, Fairbairn, L, Faulkner, GJ, Ferrai, C, Fisher, ME, Forrester, L, Goldowitz, D, Guler, R, Ha, T, Hara, M, Herlyn, M, Ikawa, T, Kai, C, Kawamoto, H, Khachigian, LM, Klinken, SP, Kojima, S, Koseki, H, Klein, S, Mejhert, N, Miyaguchi, K, Mizuno, Y, Morimoto, M, Morris, KJ, Mummery, C, Nakachi, Y, Ogishima, S, Okada-Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, D, Passier, R, Patrikakis, M, Pombo, A, Qin, X-Y, Roy, S, Sato, H, Savvi, S, Saxena, A, Schwegmann, A, Sugiyama, D, Swoboda, R, Tanaka, H, Tomoiu, A, Winteringham, LN, Wolvetang, E, Yanagi-Mizuochi, C, Yoneda, M, Zabierowski, S, Zhang, P, Abugessaisa, I, Bertin, N, Diehl, AD, Fukuda, S, Furuno, M, Harshbarger, J, Hasegawa, A, Hori, F, Ishikawa-Kato, S, Ishizu, Y, Itoh, M, Kawashima, T, Kojima, M, Kondo, N, Lizio, M, Meehan, TF, Mungall, CJ, Murata, M, Nishiyori-Sueki, H, Sahin, S, Nagao-Sato, S, Severin, J, de Hoon, MJL, Kawai, J, Kasukawa, T, Lassmann, T, Suzuki, H, Kawaji, H, Summers, KM, Wells, C, Hume, DA, Forrest, ARR, Sandelin, AG, Carninci, P & Hayashizaki, Y 2015, 'Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells', Science (New York, N.Y.), vol. 347, no. 6225, pp. 1010-1014. https://doi.org/10.1126/science.1259418

@article{263b1da9800c47df88093ddf16ebd746,

title = "Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells",

abstract = "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.",

author = "Erik Arner and Daub, {Carsten O.} and Kristoffer Vitting-Seerup and Robin Andersson and Berit Lilje and Finn Drabl{\o}s and Andreas Lennartsson and Michelle R{\"o}nnerblad and Olga Hrydziuszko and Morana Vitezic and Freeman, {Tom C} and Alhendi, {Ahmad M N} and Peter Arner and Richard Axton and Baillie, {J Kenneth} and Anthony Beckhouse and Beatrice Bodega and James Briggs and Frank Brombacher and Margaret Davis and Michael Detmar and Anna Ehrlund and Mitsuhiro Endoh and Afsaneh Eslami and Michela Fagiolini and Lynsey Fairbairn and Faulkner, {Geoffrey J} and Carmelo Ferrai and Fisher, {Malcolm E} and Lesley Forrester and Daniel Goldowitz and Reto Guler and Thomas Ha and Mitsuko Hara and Meenhard Herlyn and Tomokatsu Ikawa and Chieko Kai and Hiroshi Kawamoto and Khachigian, {Levon M} and Klinken, {S Peter} and Soichi Kojima and Haruhiko Koseki and Sarah Klein and Niklas Mejhert and Ken Miyaguchi and Yosuke Mizuno and Mitsuru Morimoto and Morris, {Kelly J} and Christine Mummery and Yutaka Nakachi and Soichi Ogishima and Mariko Okada-Hatakeyama and Yasushi Okazaki and Valerio Orlando and Dmitry Ovchinnikov and Robert Passier and Margaret Patrikakis and Ana Pombo and Xian-Yang Qin and Sugata Roy and Hiroki Sato and Suzana Savvi and Alka Saxena and Anita Schwegmann and Daisuke Sugiyama and Rolf Swoboda and Hiroshi Tanaka and Andru Tomoiu and Winteringham, {Louise N} and Ernst Wolvetang and Chiyo Yanagi-Mizuochi and Misako Yoneda and Susan Zabierowski and Peter Zhang and Imad Abugessaisa and Nicolas Bertin and Diehl, {Alexander D} and Shiro Fukuda and Masaaki Furuno and Jayson Harshbarger and Akira Hasegawa and Fumi Hori and Sachi Ishikawa-Kato and Yuri Ishizu and Masayoshi Itoh and Tsugumi Kawashima and Miki Kojima and Naoto Kondo and Marina Lizio and Meehan, {Terrence F} and Mungall, {Christopher J} and Mitsuyoshi Murata and Hiromi Nishiyori-Sueki and Serkan Sahin and Sayaka Nagao-Sato and Jessica Severin and {de Hoon}, {Michiel J L} and Jun Kawai and Takeya Kasukawa and Timo Lassmann and Harukazu Suzuki and Hideya Kawaji and Summers, {Kim M} and Christine Wells and Hume, {David A} and Forrest, {Alistair R R} and Sandelin, {Albin Gustav} and Piero Carninci and Yoshihide Hayashizaki",

note = "Copyright {\textcopyright} 2015, American Association for the Advancement of Science.",

year = "2015",

month = feb,

day = "27",

doi = "10.1126/science.1259418",

language = "English",

volume = "347",

pages = "1010--1014",

journal = "Science (New York, N.Y.)",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6225",

}

TY - JOUR

T1 - Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

AU - Arner, Erik

AU - Daub, Carsten O.

AU - Vitting-Seerup, Kristoffer

AU - Andersson, Robin

AU - Lilje, Berit

AU - Drabløs, Finn

AU - Lennartsson, Andreas

AU - Rönnerblad, Michelle

AU - Hrydziuszko, Olga

AU - Vitezic, Morana

AU - Freeman, Tom C

AU - Alhendi, Ahmad M N

AU - Arner, Peter

AU - Axton, Richard

AU - Baillie, J Kenneth

AU - Beckhouse, Anthony

AU - Bodega, Beatrice

AU - Briggs, James

AU - Brombacher, Frank

AU - Davis, Margaret

AU - Detmar, Michael

AU - Ehrlund, Anna

AU - Endoh, Mitsuhiro

AU - Eslami, Afsaneh

AU - Fagiolini, Michela

AU - Fairbairn, Lynsey

AU - Faulkner, Geoffrey J

AU - Ferrai, Carmelo

AU - Fisher, Malcolm E

AU - Forrester, Lesley

AU - Goldowitz, Daniel

AU - Guler, Reto

AU - Ha, Thomas

AU - Hara, Mitsuko

AU - Herlyn, Meenhard

AU - Ikawa, Tomokatsu

AU - Kai, Chieko

AU - Kawamoto, Hiroshi

AU - Khachigian, Levon M

AU - Klinken, S Peter

AU - Kojima, Soichi

AU - Koseki, Haruhiko

AU - Klein, Sarah

AU - Mejhert, Niklas

AU - Miyaguchi, Ken

AU - Mizuno, Yosuke

AU - Morimoto, Mitsuru

AU - Morris, Kelly J

AU - Mummery, Christine

AU - Nakachi, Yutaka

AU - Ogishima, Soichi

AU - Okada-Hatakeyama, Mariko

AU - Okazaki, Yasushi

AU - Orlando, Valerio

AU - Ovchinnikov, Dmitry

AU - Passier, Robert

AU - Patrikakis, Margaret

AU - Pombo, Ana

AU - Qin, Xian-Yang

AU - Roy, Sugata

AU - Sato, Hiroki

AU - Savvi, Suzana

AU - Saxena, Alka

AU - Schwegmann, Anita

AU - Sugiyama, Daisuke

AU - Swoboda, Rolf

AU - Tanaka, Hiroshi

AU - Tomoiu, Andru

AU - Winteringham, Louise N

AU - Wolvetang, Ernst

AU - Yanagi-Mizuochi, Chiyo

AU - Yoneda, Misako

AU - Zabierowski, Susan

AU - Zhang, Peter

AU - Abugessaisa, Imad

AU - Bertin, Nicolas

AU - Diehl, Alexander D

AU - Fukuda, Shiro

AU - Furuno, Masaaki

AU - Harshbarger, Jayson

AU - Hasegawa, Akira

AU - Hori, Fumi

AU - Ishikawa-Kato, Sachi

AU - Ishizu, Yuri

AU - Itoh, Masayoshi

AU - Kawashima, Tsugumi

AU - Kojima, Miki

AU - Kondo, Naoto

AU - Lizio, Marina

AU - Meehan, Terrence F

AU - Mungall, Christopher J

AU - Murata, Mitsuyoshi

AU - Nishiyori-Sueki, Hiromi

AU - Sahin, Serkan

AU - Nagao-Sato, Sayaka

AU - Severin, Jessica

AU - de Hoon, Michiel J L

AU - Kawai, Jun

AU - Kasukawa, Takeya

AU - Lassmann, Timo

AU - Suzuki, Harukazu

AU - Kawaji, Hideya

AU - Summers, Kim M

AU - Wells, Christine

AU - Hume, David A

AU - Forrest, Alistair R R

AU - Sandelin, Albin Gustav

AU - Carninci, Piero

AU - Hayashizaki, Yoshihide

PY - 2015/2/27

Y1 - 2015/2/27

N2 - 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.

AB - 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.

U2 - 10.1126/science.1259418

DO - 10.1126/science.1259418

M3 - Journal article

C2 - 25678556

SN - 0036-8075

VL - 347

SP - 1010

EP - 1014

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6225

ER -

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Abstract

Access to Document

Fingerprint

Cite this