The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

Genome Biology Unit, European Molecular Biology Laboratory (EMBL), D-69117 Heidelberg, Germany

Corresponding author:furlong{at}embl.de

↵3 These authors contributed equally to this work.

↵Present addresses:¹Core Unit Bioinformatics, Berlin Institute of Health, Berlin 10117, Germany;²Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Buenos Aires, Argentina.

Abstract

Gene expression is regulated by promoters, which initiate transcription, and enhancers, which control their temporal and spatial activity. However, the discovery that mammalian enhancers also initiate transcription questions the inherent differences between enhancers and promoters. Here, we investigate the transcriptional properties of enhancers duringDrosophila embryogenesis using characterized developmental enhancers. We show that while the timing of enhancer transcription is generally correlated with enhancer activity, the levels and directionality of transcription are highly varied among active enhancers. To assess how this impacts function, we developed a dual transgenic assay to simultaneously measure enhancer and promoter activities from a single element in the same embryo. Extensive transgenic analysis revealed a relationship between the direction of endogenous transcription and the ability to function as an enhancer or promoter in vivo, although enhancer RNA (eRNA) production and activity are not always strictly coupled. Some enhancers (mainly bidirectional) can act as weak promoters, producing overlapping spatio–temporal expression. Conversely, bidirectional promoters often act as strong enhancers, while unidirectional promoters generally cannot. The balance between enhancer and promoter activity is generally reflected in the levels and directionality of eRNA transcription and is likely an inherent sequence property of the elements themselves.

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Footnotes

Supplemental material is available for this article.
Article published online ahead of print. Article and publication date are online athttp://www.genesdev.org/cgi/doi/10.1101/gad.308619.117.
Freely available online through theGenes & Development Open Access option.

ReceivedOctober 23, 2017.
AcceptedDecember 21, 2017.

This article, published inGenes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described athttp://creativecommons.org/licenses/by/4.0/.