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Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation

The spatiotemporal expression of genes is controlled by enhancer sequences that bind transcription factors. Identifying the target genes of enhancers remains difficult because enhancers regulate gene expression over long genomic distances. To address this, we used an evolutionary approach to build t...

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Autores principales: Clément, Yves, Torbey, Patrick, Gilardi-Hebenstreit, Pascale, Crollius, Hugues Roest
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049698/
https://www.ncbi.nlm.nih.gov/pubmed/31943068
http://dx.doi.org/10.1093/nar/gkz1199
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author Clément, Yves
Torbey, Patrick
Gilardi-Hebenstreit, Pascale
Crollius, Hugues Roest
author_facet Clément, Yves
Torbey, Patrick
Gilardi-Hebenstreit, Pascale
Crollius, Hugues Roest
author_sort Clément, Yves
collection PubMed
description The spatiotemporal expression of genes is controlled by enhancer sequences that bind transcription factors. Identifying the target genes of enhancers remains difficult because enhancers regulate gene expression over long genomic distances. To address this, we used an evolutionary approach to build two genome-wide maps of predicted enhancer–gene associations in the human and zebrafish genomes. Evolutionary conserved sequences were linked to their predicted target genes using PEGASUS, a bioinformatics method that relies on evolutionary conservation of synteny. The analysis of these maps revealed that the number of predicted enhancers linked to a gene correlate with its expression breadth. Comparison of both maps identified hundreds of putative vertebrate ancestral regulatory relationships from which we could determine that predicted enhancer–gene distances scale with genome size despite strong positional conservation. The two maps represent a resource for further studies, including the prioritization of sequence variants in whole genome sequence of patients affected by genetic diseases.
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spelling pubmed-70496982020-03-10 Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation Clément, Yves Torbey, Patrick Gilardi-Hebenstreit, Pascale Crollius, Hugues Roest Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The spatiotemporal expression of genes is controlled by enhancer sequences that bind transcription factors. Identifying the target genes of enhancers remains difficult because enhancers regulate gene expression over long genomic distances. To address this, we used an evolutionary approach to build two genome-wide maps of predicted enhancer–gene associations in the human and zebrafish genomes. Evolutionary conserved sequences were linked to their predicted target genes using PEGASUS, a bioinformatics method that relies on evolutionary conservation of synteny. The analysis of these maps revealed that the number of predicted enhancers linked to a gene correlate with its expression breadth. Comparison of both maps identified hundreds of putative vertebrate ancestral regulatory relationships from which we could determine that predicted enhancer–gene distances scale with genome size despite strong positional conservation. The two maps represent a resource for further studies, including the prioritization of sequence variants in whole genome sequence of patients affected by genetic diseases. Oxford University Press 2020-03-18 2020-01-16 /pmc/articles/PMC7049698/ /pubmed/31943068 http://dx.doi.org/10.1093/nar/gkz1199 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Clément, Yves
Torbey, Patrick
Gilardi-Hebenstreit, Pascale
Crollius, Hugues Roest
Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
title Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
title_full Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
title_fullStr Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
title_full_unstemmed Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
title_short Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
title_sort enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049698/
https://www.ncbi.nlm.nih.gov/pubmed/31943068
http://dx.doi.org/10.1093/nar/gkz1199
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