PT  - JOURNAL ARTICLE
AU  - Yves Clément
AU  - Patrick Torbey
AU  - Pascale Gilardi-Hebenstreit
AU  - Hugues Roest Crollius
TI  - Enhancer-gene maps in the human and zebrafish genomes using evolutionary linkage conservation
AID  - 10.1101/244475
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 244475
4099  - http://biorxiv.org/content/early/2018/11/22/244475.short
4100  - http://biorxiv.org/content/early/2018/11/22/244475.full
AB  - 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 enhancer-gene associations in the human and zebrafish genomes. Enhancers were identified using sequence conservation, and 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 enhancers linked to a gene correlate with its expression breadth. Comparison of both maps identified hundreds of vertebrate ancestral regulatory relationships from which we could determine that enhancer-gene distances scale with genome size despite strong positional conservation. The two maps represent a resource for further studies, including the prioritisation of sequence variants in whole genome sequence of patients affected by genetic diseases.