Back to Search
Start Over
Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome
- Source :
- Nature Communications, 6, 6904, Nature Communications, Nature Communications, Nature Publishing Group, 2015, 6, pp.6904. ⟨10.1038/ncomms7904⟩, 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, Straehle, U, Lenhard, B, Bally-Cuif, L, van Heyningen, V, FitzPatrick, D R, Becker, T S & Crollius, H R 2015, ' Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome ', Nature Communications, vol. 6, 6904 . https://doi.org/10.1038/ncomms7904
- Publication Year :
- 2015
- Publisher :
- Karlsruhe, 2015.
-
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.<br />Enhancers regulate the transcription of genes over long genomic distances. Here, the authors show that enhancer function is correlated with maintenance of linkage between non-coding elements and neighbouring genes in the human X chromosome and that enhancers in zebrafish drive expression in a pattern consistent with the expression of a linked gene.
- Subjects :
- Life sciences
biology
Genetic Linkage
DATABASE
Evolution
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Gene Expression
Article
DISEASE
Animals, Genetically Modified
Evolution, Molecular
Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714 [VDP]
Medisinske Fag: 700 [VDP]
ddc:570
ELEMENTS
Genetics
Animals
Humans
Selection, Genetic
Zebrafish
GENE-EXPRESSION
Gene Rearrangement
TOOLS
Chromosomes, Human, X
[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
GENOMIC SEQUENCES
IN-SITU HYBRIDIZATION
ENHANCERS
Biological sciences
Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP]
Enhancer Elements, Genetic
HUMAN CELL-TYPES
CONSERVED SYNTENY
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, 6, 6904, Nature Communications, Nature Communications, Nature Publishing Group, 2015, 6, pp.6904. ⟨10.1038/ncomms7904⟩, 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, Straehle, U, Lenhard, B, Bally-Cuif, L, van Heyningen, V, FitzPatrick, D R, Becker, T S & Crollius, H R 2015, ' Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome ', Nature Communications, vol. 6, 6904 . https://doi.org/10.1038/ncomms7904
- Accession number :
- edsair.doi.dedup.....6784feec55aaca02d6c4d7914efc6f9d
- Full Text :
- https://doi.org/10.5445/ir/110102528