Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Arner, E. et al. (2015) Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science, 347(6255), pp. 101-1014. (doi: 10.1126/science.1259418) (PMID:25678556)

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Abstract

While 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 mRNAs encoding transcription factors dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously over-represented 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wells, Dr Christine and Forrester, Dr Lesley
Authors: Arner, E., Daub, C. O., Vitting-Seerup, K., Andersson, R., Lilje, B., Drablos, F., Lennartsson, A., Ronnerblad, M., Hrydziuszko, O., Vitezic, M., Freeman, T. C., Alhendi, A., Arner, P., Axton, R., Baillie, J. K., Beckhouse, A., Bodega, B., Briggs, J., Brombacher, F., Davis, M., Detmar, M., Ehrlund, A., Endoh, M., Eslami, A., Fagiolini, M., Fairbairn, L., Faulkner, G. J., Ferrai, C., Fisher, M. E., Forrester, L., Goldowitz, D., Guler, R., Ha, T., Hara, M., Herlyn, M., Ikawa, T., Kai, C., Kawamoto, H., Khachigian, L., Klinken, P. S., Kojima, S., Koseki, H., Klein, S., Mejhert, N., Miyaguchi, K., Mizuno, Y., Morimoto, M., Morris, K. J., 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, N., Sugiyama, D., Swoboda, R., Tanaka, H., Tomoiu, A., Winteringham, L. N., Wolvetang, E., Yanagi-Mizuochi, C., Yoneda, M., Zabierowski, S., Zhang, P., Abugessaisa, I., Bertin, N., Diehl, A. D., 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, T. F., Mungall, C. J., Murata, M., Nishiyori-Sueki, H., Sahin, S., Sato-Nagao, S., Severin, J., de Hoon, M. J. L., Kawai, J., Kasukawa, T., Lassmann, T., Suzuki, H., Kawaji, H., Summers, K. M., Wells, C., Hume, D. A., Forrest, A. R., Sandelin, A., Carninci, P., and Hayashizaki, Y.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Science
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
ISSN (Online):1095-9203

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