BMC Genomics | |
Genetic and epigenetic regulation of gene expression in fetal and adult human livers | |
Lili Milani8  Lude Franke6  Magnus Ingelman-Sundberg7  Alexandra Zhernakova6  Cisca Wijmenga6  Marten H Hofker1  Jingyuan Fu6  Marcel G Wolfs1  Jana V van Vliet-Ostaptchouk9  Sander S Rensen2  Maxim Ivanov7  Jan-Willem Greve3  Patrick Deelen5  Wim A Buurman2  Isabel Barragan7  Kaie Lokk4  Riin Tamm4  Mart Kals1,10  Silva Kasela4  Marc Jan Bonder6  | |
[1] University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Molecular Genetics section, Groningen, the Netherlands;Department of Surgery, University Hospital Maastricht and Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, Maastricht, the Netherlands;Department of General Surgery, Atrium Medical Center Parkstad, Heerlen, the Netherlands;Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia;University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands;University of Groningen, University Medical Center Groningen, Department of Genetics, Hanzeplein 1, 9700 RB Groningen, the Netherlands;Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden;Estonian Genome Center, University of Tartu, Riia 23 B, 51010 Tartu, Estonia;University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, the Netherlands;Institute of Mathematical Statistics, University of Tartu, Tartu, Estonia | |
关键词: Liver; HumanMethylation450; Methylation; Gene expression; eQTM; meQTL; eQTL; | |
Others : 1136335 DOI : 10.1186/1471-2164-15-860 |
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received in 2014-05-19, accepted in 2014-09-24, 发布年份 2014 | |
【 摘 要 】
Background
The 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.
Results
By 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.
Conclusions
Our 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.
【 授权许可】
2014 Bonder et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
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20150312051316374.pdf | 1047KB | download | |
Figure 4. | 142KB | Image | download |
Figure 3. | 41KB | Image | download |
Figure 2. | 75KB | Image | download |
Figure 1. | 52KB | Image | download |
【 图 表 】
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