The effect of genetic variation on promoter usage and enhancer activity.

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Serval ID
serval:BIB_B40AB423111C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The effect of genetic variation on promoter usage and enhancer activity.
Journal
Nature Communications
Author(s)
Garieri M., Delaneau O., Santoni F., Fish R.J., Mull D., Carninci P., Dermitzakis E.T., Antonarakis S.E., Fort A.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
8
Number
1
Pages
1358
Language
english
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.

Pubmed
Web of science
Open Access
Yes
Create date
15/11/2017 8:35
Last modification date
29/02/2020 6:26
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