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Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns

Please always quote using this URN: urn:nbn:de:bvb:20-opus-68371
  • DNA methylation is an epigenetic modification that plays an important role in gene regulation. It can be influenced by stochastic events, environmental factors and developmental programs. However, little is known about the natural variation of genespecific methylation patterns. In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus,DNA methylation is an epigenetic modification that plays an important role in gene regulation. It can be influenced by stochastic events, environmental factors and developmental programs. However, little is known about the natural variation of genespecific methylation patterns. In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus, fetal and adult cortex, and adult blood samples. Both average methylation level and range of methylation variation depended on the gene locus, tissue type and/or developmental stage. We found considerable variability of functionally important methylation patterns among unrelated healthy individuals and a trend toward more similar methylation levels in monozygotic twins than in dizygotic twins. Imprinted genes showed relatively little methylation changes associated with aging in individuals who are >25 years. The relative differences in methylation among neighboring CpGs in the generally hypomethylated APC promoter may not only reflect stochastic fluctuations but also depend on the tissue type. Our results are consistent with the view that most methylation variation may arise after fertilization, leading to epigenetic mosaicism.show moreshow less

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Metadaten
Author: Eberhard Schneider, Galyna Pliushch, Nady El Hajj, Danuta Galetzka, Alexander Puhl, Martin Schorsch, Katrin Frauenknecht, Thomas Riepert, Achim Tresch, Annette M. Mueller, Wiltrud Coerdt, Ulrich Zechner, Thomas Haaf
URN:urn:nbn:de:bvb:20-opus-68371
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Humangenetik
Language:English
Year of Completion:2010
Source:In: Nucleic Acids Research (2010) 38, 12, 3880-3890, DOI: 10.1093/nar/gkq126
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Medizin
Release Date:2012/11/10
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung