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Enhancer-gene maps in the human and zebrafish genomes using evolutionary linkage conservation
Yves Clément1, Patrick Torbey1, Pascale Gilardi-Hebenstreit1
1École Normale Supérieure, PSL Research University, CNRS, Inserm, Institut de Biologie de l'École Normale Supérieure (IBENS), F-75005 Paris, France.
Nucleic Acids Research
|January 17, 2020
Summary
Scientists mapped gene regulatory elements called enhancers to their target genes using evolutionary conservation. This enhancer-gene map aids in understanding gene expression and prioritizing genetic variants in diseases.
Area of Science:
- Genomics
- Bioinformatics
- Evolutionary Biology
Background:
- Gene expression spatiotemporal control relies on enhancer sequences binding transcription factors.
- Identifying enhancer-target gene relationships is challenging due to long genomic distances involved in gene regulation.
Purpose of the Study:
- To develop genome-wide maps of predicted enhancer-gene associations in humans and zebrafish.
- To leverage evolutionary conservation to predict enhancer-gene links and analyze regulatory relationships.
Main Methods:
- Utilized an evolutionary approach to construct enhancer-gene association maps.
- Employed PEGASUS, a bioinformatics method using conserved synteny, to link evolutionary conserved sequences to target genes.
- Analyzed human and zebrafish genomes.
Main Results:
- Developed two genome-wide maps of predicted enhancer-gene associations.
- Found that the number of enhancers linked to a gene correlates with its expression breadth.
- Identified hundreds of putative ancestral vertebrate regulatory relationships.
- Determined that enhancer-gene distances scale with genome size despite positional conservation.
Conclusions:
- The created enhancer-gene maps are valuable resources for biological research.
- These maps can aid in prioritizing sequence variants for genetic disease studies.
- The findings provide insights into the evolution of gene regulatory networks.
