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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, T.A.; Wilson, S.W.; Manning, E.; Chilamakuri, C.S.R.; Wilson, D.I.; Louis, A.; Raymond, F.L.; Rastegar, S.; Strähle, U.; Lenhard, B.; Bally-Cuif, L.; van Heyningen, V.; FitzPatrick, D.R.; Becker, T.S.; ... mehr

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.


Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Jahr 2015
Sprache Englisch
Identifikator DOI: 10.1038/ncomms7904
ISSN: 2041-1723
URN: urn:nbn:de:swb:90-AAA1101025283
KITopen ID: 110102528
HGF-Programm 47.01.01; LK 01
Erschienen in Nature Communications
Band 6
Seiten 6904
Lizenz CC BY 4.0: Creative Commons Namensnennung 4.0 International
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