PUBLICATION

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

Authors
Naville, M., Ishibashi, M., Ferg, M., Bengani, H., Rinkwitz, S., Krecsmarik, M., Hawkins, T.A., Wilson, S.W., Manning, E., Chilamakuri, C.S., Wilson, D.I., Louis, A., Lucy Raymond, F., Rastegar, S., Strähle, U., Lenhard, B., Bally-Cuif, L., van Heyningen, V., FitzPatrick, D.R., Becker, T.S., Roest Crollius, H.
ID
ZDB-PUB-150425-5
Date
2015
Source
Nature communications   6: 6904 (Journal)
Registered Authors
Bally-Cuif, Laure, Becker, Thomas S., Ferg, Marco, Hawkins, Tom, Ishibashi, Minaka, Manning, Liz, Rastegar, Sepand, Rinkwitz, Silke, Strähle, Uwe, van Heyningen, Veronica, Wilson, Steve
Keywords
Disease genetics, Evolutionary genetics
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Chromosomes, Human, X/genetics*
  • Enhancer Elements, Genetic/genetics*
  • Evolution, Molecular
  • Gene Expression/genetics*
  • Gene Rearrangement/genetics
  • Genetic Linkage/genetics*
  • Humans
  • Selection, Genetic/genetics*
  • Zebrafish
PubMed
25908307 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes