cis -Acting Complex-Trait-Associated lincRNA Expression Correlates with Modulation of Chromosomal Architecture
| Autor: | Sven Bergmann, Reyhan Sonmez, Cyril Matthey-Doret, Rico Rueedi, Adam Alexander T. Smith, Maria Ferreira da Silva, Ana C. Marques, David Ding, Zoltán Kutalik, Jennifer Y. Tan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Quantitative Trait Loci Gene Expression Genome-wide association study Quantitative trait locus Biology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Chromosomes Cell Line 03 medical and health sciences Mice Cell Line Tumor Human Umbilical Vein Endothelial Cells Animals Humans Chromatin/genetics Chromosomes/genetics Gene Expression/genetics Gene Expression Regulation/genetics K562 Cells 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 Enhancer lcsh:QH301-705.5 Genetics Regulation of gene expression Chromatin 030104 developmental biology lcsh:Biology (General) Gene Expression Regulation CTCF Expression quantitative trait loci Human genome RNA Long Noncoding |
| Zdroj: | Cell Reports, Vol 18, Iss 9, Pp 2280-2288 (2017) Cell reports, vol. 18, no. 9, pp. 2280-2288 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2017.02.009 |
| Popis: | Summary: 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. : Tan et al. identify and characterize 69 human complex trait/disease-associated lincRNAs in LCLs. They show that these loci are often associated with cis-regulation of gene expression and tend to be localized at TAD boundaries, suggesting that these lincRNAs may influence chromosomal architecture. Keywords: intergenic long noncoding RNA, lincRNA, GWAS, expression quantitative trait loci, eQTL, complex trait and disease, enhancer, cis-regulation, topologically associated domains, TAD |
| Databáze: | OpenAIRE |
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