Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25908307.
- Also identified by DOI 10.1038/ncomms7904 and PMC identifier 4423230.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Chromosomes, Human, X
- Enhancer Elements, Genetic
- Gene Expression
- Genetic Linkage
- Selection, Genetic