Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome.
Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome.
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DOI：
10.1038/ncomms7904
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发表时间：
2015-04-24
影响因子：
16.6
通讯作者：
Roest Crollius H
中科院分区：
文献类型：
--
作者：
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
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. 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.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
7
作者：
Kikuta, Hiroshi;Laplante, Mary;Becker, Thomas S.
通讯作者：
Becker, Thomas S.
影响因子：
4.6
作者：
Rothenaigner, Ina;Krecsmarik, Monika;Bally-Cuif, Laure
通讯作者：
Bally-Cuif, Laure
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影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
影响因子：
30.8
作者：
Benko, Sabina;Fantes, Judy A.;Lyonnet, Stanislas
通讯作者：
Lyonnet, Stanislas