On the importance of evolutionary constraint for regulatory sequence identification

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Giudicelli, François | Roest Crollius, Hugues

Edité par CCSD ; Oxford University Press -

International audience. Regulation of gene expression relies on the activity of specialized genomic elements, enhancers or silencers, distributed over sometimes large distance from their target gene promoters. A significant part of vertebrate genomes consists in such regulatory elements, but their identification and that of their target genes remains challenging, due to the lack of clear signature at the nucleotide level. For many years the main hallmark used for identifying functional elements has been their sequence conservation between genomes of distant species, indicative of purifying selection. More recently, genome-wide biochemical assays have opened new avenues for detecting regulatory regions, shifting attention away from evolutionary constraints. Here, we review the respective contributions of comparative genomics and biochemical assays for the definition of regulatory elements and their targets and advocate that both sequence conservation and preserved synteny, taken as signature of functional constraint, remain essential tools in this task.

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