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, Andru Tomoiu, Kim M Summers, FANTOM Consortium, David A Hume

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)1010-1014
Number of pages5
Issue number6225
Early online date12 Feb 2015
Publication statusPublished - 27 Feb 2015


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