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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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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. |
format | Online Article Text |
id | pubmed-7049698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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