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

Naville, M; Ishibashi, M; Ferg, M; Bengani, H; Rinkwitz, S; Krecsmarik, M; Hawkins, TA; ... Roest Crollius, H; + view all (2015) Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome. Nat Commun , 6 , Article 6904. 10.1038/ncomms7904. Green open access

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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.

Type: Article
Title: Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms7904
Publisher version: http://dx.doi.org/10.1038/ncomms7904
Language: English
Additional information: Copyright © 2015 Macmillan Publishers Limited. All rights reserved.This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1463934
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