Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns.
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 gene-specific 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.
Schneider
Eberhard
E
Institute of Human Genetics, Julius Maximilians University, Biozentrum, Am Hubland, 97074 Wuerzburg, Germany.
Pliushch
Galyna
G
El Hajj
Nady
N
Galetzka
Danuta
D
Puhl
Alexander
A
Schorsch
Martin
M
Frauenknecht
Katrin
K
Riepert
Thomas
T
Tresch
Achim
A
Müller
Annette M
AM
Coerdt
Wiltrud
W
Zechner
Ulrich
U
Haaf
Thomas
T
D000367:Age Factors; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D014644:Genetic Variation; D018392:Genomic Imprinting; D048788:Growth and Development / Q000235:genetics; D006801:Humans; D008297:Male; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic