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© Marion Coolen
Radial glia neural stem cells of the adult zebrafish telencephalon electroporated with a membrane tagged GFP
Publication : Nature communications

Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 24 Apr 2015

Naville M, Ishibashi M, Ferg M, Bengani H, Rinkwitz S, Krecsmarik M, Hawkins TA, Wilson SW, Manning E, Chilamakuri CS, Wilson DI, Louis A, Lucy Raymond F, Rastegar S, Strähle U, Lenhard B, Bally-Cuif L, van Heyningen V, FitzPatrick DR, Becker TS, Roest Crollius H

Link to Pubmed [PMID] – 25908307

Nat Commun 2015;6:6904

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.

http://www.ncbi.nlm.nih.gov/pubmed/25908307