| Literature DB >> 29116076 |
Marco Garieri1,2,3, Olivier Delaneau1,2,3, Federico Santoni1,4, Richard J Fish1, David Mull1, Piero Carninci5, Emmanouil T Dermitzakis1,2,3, Stylianos E Antonarakis1,2,4, Alexandre Fort6.
Abstract
The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains challenging. Here, we use natural genetic variation and CAGE transcriptomes from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals, to map 5376 and 110 regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs), respectively. We characterize five categories of genes associated with puQTLs, distinguishing single from multi-promoter genes. Among multi-promoter genes, we find puQTL effects either specific to a single promoter or to multiple promoters with variable effect orientations. Regulatory variants associated with opposite effects on different mRNA isoforms suggest compensatory mechanisms occurring between alternative promoters. Our analyses identify differential promoter usage and modulation of enhancer activity as molecular mechanisms underlying eQTLs related to regulatory elements.Entities:
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Year: 2017 PMID： 29116076 PMCID： PMC5677018 DOI： 10.1038/s41467-017-01467-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919