The emerging landscape of dynamic DNA methylation in early childhood

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Xu, Cheng-Jian ; Bonder, Marc Jan ; Soderhall, Cilla ; Bustamante, Mariona ; Baiz, Nour ; Gehring, Ulrike ; Jankipersadsing, Soesma A. ; van der Vlies, Pieter ; van Diemen, Cleo C. ; van Rijkom, Bianca ; Just, Jocelyne ; Kull, Inger ; Kere, Juha ; Anto, Josep Maria ; Bousquet, Jean ; Zhernakova, Alexandra ; Wijmenga, Cisca ; Annesi-Maesano, Isabella ; Sunyer, Jordi ; Melen, Erik ; Li, Yang ; Postma, Dirkje S. ; Koppelman, Gerard H.

• Tipo de documento: Artigo Científico
• Fonte: BMC Genomics; v. 18, JAN 5 2017.
• Citações Web of Science: 16

Resumo

Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood. Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of rho < 1.14x10(-7). Genes with an increase in age-differential methylation were enriched in pathways related to `development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease. Conclusion: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life. (AU)

• Processo FAPESP: 12/51290-6 - A amamentação pode ajudar na prevenção de doenças alérgicas? Papel da presença de alérgenos, TGF-beta e anticorpos específicos IgG e IgA no colostro
• Beneficiário: Patricia Macchiaverni
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado