Genetic and epigenetic regulation of gene expression in fetal and adult human livers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-10-04

AUTHORS

Marc Jan Bonder, Silva Kasela, Mart Kals, Riin Tamm, Kaie Lokk, Isabel Barragan, Wim A Buurman, Patrick Deelen, Jan-Willem Greve, Maxim Ivanov, Sander S Rensen, Jana V van Vliet-Ostaptchouk, Marcel G Wolfs, Jingyuan Fu, Marten H Hofker, Cisca Wijmenga, Alexandra Zhernakova, Magnus Ingelman-Sundberg, Lude Franke, Lili Milani

ABSTRACT

BackgroundThe liver plays a central role in the maintenance of homeostasis and health in general. However, there is substantial inter-individual variation in hepatic gene expression, and although numerous genetic factors have been identified, less is known about the epigenetic factors.ResultsBy analyzing the methylomes and transcriptomes of 14 fetal and 181 adult livers, we identified 657 differentially methylated genes with adult-specific expression, these genes were enriched for transcription factor binding sites of HNF1A and HNF4A. We also identified 1,000 genes specific to fetal liver, which were enriched for GATA1, STAT5A, STAT5B and YY1 binding sites. We saw strong liver-specific effects of single nucleotide polymorphisms on both methylation levels (28,447 unique CpG sites (meQTL)) and gene expression levels (526 unique genes (eQTL)), at a false discovery rate (FDR) < 0.05. Of the 526 unique eQTL associated genes, 293 correlated significantly not only with genetic variation but also with methylation levels. The tissue-specificities of these associations were analyzed in muscle, subcutaneous adipose tissue and visceral adipose tissue. We observed that meQTL were more stable between tissues than eQTL and a very strong tissue-specificity for the identified associations between CpG methylation and gene expression.ConclusionsOur analyses generated a comprehensive resource of factors involved in the regulation of hepatic gene expression, and allowed us to estimate the proportion of variation in gene expression that could be attributed to genetic and epigenetic variation, both crucial to understanding differences in drug response and the etiology of liver diseases. More... »

PAGES

860

References to SciGraph publications

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  • Journal

    TITLE

    BMC Genomics

    ISSUE

    1

    VOLUME

    15

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1471-2164-15-860

    DOI

    http://dx.doi.org/10.1186/1471-2164-15-860

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004124398

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25282492


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