Enhancers with tissue-specific activity are enriched in intronic regions
- Beatrice Borsari1,6,
- Pablo Villegas-Mirón2,6,
- Sílvia Pérez-Lluch1,
- Isabel Turpin2,
- Hafid Laayouni2,3,
- Alba Segarra-Casas2,
- Jaume Bertranpetit2,
- Roderic Guigó1,4 and
- Sandra Acosta2,5
- 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona 08003, Catalonia, Spain;
- 2Institut de Biologia Evolutiva (UPF-CSIC), Universitat Pompeu Fabra, Barcelona 08003, Catalonia, Spain;
- 3Bioinformatic Studies, ESCI-UPF, 08003, Barcelona, Spain;
- 4Universitat Pompeu Fabra (UPF), Barcelona 08003, Catalonia, Spain;
- 5Department of Pathology and Experimental Therapeutics, Medical School, University of Barcelona, 08907, L'Hospitalet de Llobregat, Catalonia, Spain
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↵6 These authors contributed equally to this work.
Abstract
Tissue function and homeostasis reflect the gene expression signature by which the combination of ubiquitous and tissue-specific genes contribute to the tissue maintenance and stimuli-responsive function. Enhancers are central to control this tissue-specific gene expression pattern. Here, we explore the correlation between the genomic location of enhancers and their role in tissue-specific gene expression. We find that enhancers showing tissue-specific activity are highly enriched in intronic regions and regulate the expression of genes involved in tissue-specific functions, whereas housekeeping genes are more often controlled by intergenic enhancers, common to many tissues. Notably, an intergenic-to-intronic active enhancers continuum is observed in the transition from developmental to adult stages: the most differentiated tissues present higher rates of intronic enhancers, whereas the lowest rates are observed in embryonic stem cells. Altogether, our results suggest that the genomic location of active enhancers is key for the tissue-specific control of gene expression.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.270371.120.
- Received August 21, 2020.
- Accepted June 23, 2021.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
