Interindividual variability and co-regulation of DNA methylation differ among blood cell populations
| Autor: | Sandra Gohrbandt, Victor Clausse, Nicolaas H. C. Brons, Claude P. Muller, Monique Jacoby |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Cancer Research Adolescent Population Lipopolysaccharide Receptors Biology Peripheral blood mononuclear cell Blood cell Interferon-gamma Young Adult medicine Humans Promoter Regions Genetic education Molecular Biology education.field_of_study Infant Newborn Promoter Methylation DNA Methylation Middle Aged Fetal Blood Molecular biology medicine.anatomical_structure CpG site Cord blood DNA methylation Leukocytes Mononuclear Regression Analysis CpG Islands Female Research Paper |
| Zdroj: | Epigenetics. 7:1421-1434 |
| ISSN: | 1559-2308 1559-2294 |
| DOI: | 10.4161/epi.22845 |
| Popis: | DNA methylation regulates gene expression in a cell-type specific way. Although peripheral blood mononuclear cells (PBMCs) comprise a heterogeneous cell population, most studies of DNA methylation in blood are performed on total mononuclear cells. In this study, we investigated high resolution methylation profiles of 58 CpG sites dispersed over eight immune response genes in multiple purified blood cells from healthy adults and newborns. Adjacent CpG sites showed methylation levels that were increasingly correlated in adult blood vs. cord blood. Thus, while interindividual variability increases from newborn to adult blood, the underlying methylation changes may not be merely stochastic, but seem to be orchestrated as clusters of adjacent CpG sites. Multiple linear regression analysis showed that interindividual methylation variability was influenced by distance of average methylation levels to the closest border (0 or 100%), presence of transcription factor binding sites, CpG conservation across species and age. Furthermore, CD4+ and CD14+ cell types were negative predictors of methylation variability. Concerns that PBMC methylation differences may be confounded by variations in blood cell composition were justified for CpG sites with large methylation differences across cell types, such as in the IFN-γ gene promoter. Taken together, our data suggest that unsorted mononuclear cells are reasonable surrogates of CD8+ and, to a lesser extent, CD4+ T cell methylation in adult peripheral, but not in neonatal, cord blood. |
| Databáze: | OpenAIRE |
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