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Center of Excellence In Genomic Medicine Research
Document Details
Document Type
:
Article In Journal
Document Title
:
Genetic and epigenetic regulation of human lincRNA gene expression
Genetic and epigenetic regulation of human lincRNA gene expression
Document Language
:
English
Abstract
:
Large intergenic noncoding RNAs (lincRNAs) are still poorly functionally characterized. We analyzed the genetic and epigenetic regulation of human lincRNA expression in the GenCord collection by using three cell types from 195 unrelated European individuals. We detected a considerable number of cis expression quantitative trait loci (cis-eQTLs) and demonstrated that the genetic regulation of lincRNA expression is independent of the regulation of neighboring protein-coding genes. lincRNAs have relatively more cis-eQTLs than do equally expressed protein-coding genes with the same exon number. lincRNA cis-eQTLs are located closer to transcription start sites (TSSs) and their effect sizes are higher than cis-eQTLs found for protein-coding genes, suggesting that lincRNA expression levels are less constrained than that of protein-coding genes. Additionally, lincRNA cis-eQTLs can influence the expression level of nearby protein-coding genes and thus could be considered as QTLs for enhancer activity. Enrichment of expressed lincRNA promoters in enhancer marks provides an additional argument for the involvement of lincRNAs in the regulation of transcription in cis. By investigating the epigenetic regulation of lincRNAs, we observed both positive and negative correlations between DNA methylation and gene expression (expression quantitative trait methylation [eQTMs]), as expected, and found that the landscapes of passive and active roles of DNA methylation in gene regulation are similar to protein-coding genes. However, lincRNA eQTMs are located closer to TSSs than are protein-coding gene eQTMs. These similarities and differences in genetic and epigenetic regulation between lincRNAs and protein-coding genes contribute to the elucidation of potential functions of lincRNAs.
ISSN
:
0002-9297
Journal Name
:
The American Journal of Human Genetics
Volume
:
93
Issue Number
:
6
Publishing Year
:
1434 AH
2013 AD
Article Type
:
Article
Added Date
:
Thursday, March 10, 2016
Researchers
Researcher Name (Arabic)
Researcher Name (English)
Researcher Type
Dr Grade
Email
Konstantin Popadin
Popadin, Konstantin
Investigator
Maria Gutierrez-Arcelus
Gutierrez-Arcelus, Maria
Researcher
Emmanouil T Dermitzakis
Dermitzakis, Emmanouil T
Researcher
Stylianos E Antonarakis
Antonarakis, Stylianos E
Researcher
Files
File Name
Type
Description
38389.pdf
pdf
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