Methylomics of gene expression in human monocytes
| Autor: | R. Graham Barr, Alberto de la Fuente, Jessica Morris, David M. Herrington, Charles E. McCall, Joel D. Kaufman, Russell P. Tracy, Wei Cui, David R. Jacobs, G.A. Hawkins, Shelly G. Smith, David Siscovick, Ina Hoeschele, Yongmei Liu, Timothy D. Howard, Wendy Post, Jingzhong Ding, Kurt Lohman, Steven Shea, Lindsay M. Reynolds, Thomas C. Register, Gregory L. Burke |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Bisulfite sequencing Regulatory Sequences Nucleic Acid Biology Polymorphism Single Nucleotide Monocytes Epigenesis Genetic Epigenetics of physical exercise Genetics Humans Molecular Biology RNA-Directed DNA Methylation Genetics (clinical) Aged Glutathione Transferase Epigenomics Aged 80 and over Regulation of gene expression Gene Expression Profiling Association Studies Articles Molecular Sequence Annotation General Medicine DNA Methylation Middle Aged Atherosclerosis Molecular biology Gene Expression Regulation CpG site DNA methylation Illumina Methylation Assay CpG Islands Female Transcription Initiation Site Transcriptome Genome-Wide Association Study |
| Zdroj: | Human Molecular Genetics. 22:5065-5074 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | DNA methylation is one of several epigenetic mechanisms that contribute to the regulation of gene expression; however, the extent to which methylation of CpG dinucleotides correlates with gene expression at the genome-wide level is still largely unknown. Using purified primary monocytes from subjects in a large community-based cohort (n = 1264), we characterized methylation (>485 000 CpG sites) and mRNA expression (>48K transcripts) and carried out genome-wide association analyses of 8370 expression phenotypes. We identified 11 203 potential cis-acting CpG loci whose degree of methylation was associated with gene expression (eMS) at a false discovery rate threshold of 0.001. Most of the associations were consistent in effect size and direction of effect across sex and three ethnicities. Contrary to expectation, these eMS were not predominately enriched in promoter regions, or CpG islands, but rather in the 3' UTR, gene bodies, CpG shores or 'offshore' sites, and both positive and negative correlations between methylation and expression were observed across all locations. eMS were enriched for regions predicted to be regulatory by ENCODE (Encyclopedia of DNA Elements) data in multiple cell types, particularly enhancers. One of the strongest association signals detected (P < 2.2 × 10(-308)) was a methylation probe (cg17005068) in the promoter/enhancer region of the glutathione S-transferase theta 1 gene (GSTT1, encoding the detoxification enzyme) with GSTT1 mRNA expression. Our study provides a detailed description of the epigenetic architecture in human monocytes and its relationship to gene expression. These data may help prioritize interrogation of biologically relevant methylation loci and provide new insights into the epigenetic basis of human health and diseases. |
| Databáze: | OpenAIRE |
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