cis-Acting Complex-Trait-Associated lincRNA Expression Correlates with Modulation of Chromosomal Architecture.

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Version: Final published version
Serval ID
serval:BIB_3FE7271DEEFD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
cis-Acting Complex-Trait-Associated lincRNA Expression Correlates with Modulation of Chromosomal Architecture.
Journal
Cell reports
Author(s)
Tan J.Y., Smith AAT, Ferreira da Silva M., Matthey-Doret C., Rueedi R., Sönmez R., Ding D., Kutalik Z., Bergmann S., Marques A.C.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
28/02/2017
Peer-reviewed
Oui
Volume
18
Number
9
Pages
2280-2288
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Intergenic long noncoding RNAs (lincRNAs) are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs) in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain (TAD) boundaries provide evidence that TR-lincRNAs likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between TR-lincRNA abundance and intra-TAD DNA-DNA contacts. Our results provide insights into the molecular mode of action by which TR-lincRNAs contribute to complex human traits.

Keywords
Animals, Cell Line, Cell Line, Tumor, Chromatin/genetics, Chromosomes/genetics, Gene Expression/genetics, Gene Expression Regulation/genetics, Human Umbilical Vein Endothelial Cells, Humans, K562 Cells, Mice, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, RNA, Long Noncoding/genetics, GWAS, TAD, cis-regulation, complex trait and disease, eQTL, enhancer, expression quantitative trait loci, intergenic long noncoding RNA, lincRNA, topologically associated domains
Pubmed
Web of science
Open Access
Yes
Create date
07/03/2017 19:23
Last modification date
20/08/2019 14:37
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