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Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. Here we test this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved noncoding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with this linkage score. We test >1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene. The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression.

Original publication

DOI

10.1038/ncomms7904

Type

Journal article

Journal

Nat Commun

Publication Date

24/04/2015

Volume

6

Keywords

Animals, Animals, Genetically Modified, Chromosomes, Human, X, Enhancer Elements, Genetic, Evolution, Molecular, Gene Expression, Gene Rearrangement, Genetic Linkage, Humans, Selection, Genetic, Zebrafish