Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta.

Abstract:

BACKGROUND:Epigenetics is tissue-specific and potentially even cell-specific, but little information is available from human reproductive studies about the concordance of DNA methylation patterns in cord blood and placenta, as well as within-placenta variations. We evaluated methylation levels at promoter regions of candidate genes in biological ageing pathways (SIRT1, TP53, PPARG, PPARGC1A, and TFAM), a subtelomeric region (D4Z4) and the mitochondrial genome (MT-RNR1, D-loop). METHODS:Ninety individuals were randomly chosen from the ENVIRONAGE birth cohort to evaluate methylation concordance between cord blood and placenta using highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen individuals, a more extensive sampling scheme was performed to examine within-placenta variation. RESULTS:The DNA methylation levels of the subtelomeric region and mitochondrial genome showed concordance between cord blood and placenta with correlation coefficients ranging from r = 0.31 to 0.43, p ≤ 0.005, and also between the maternal and foetal sides of placental tissue (r = 0.53 to 0.72, p ≤ 0.05). For the majority of targets, an agreement in methylation levels between four foetal biopsies was found (with intra-class correlation coefficients ranging from 0.16 to 0.72), indicating small within-placenta variation. CONCLUSIONS:The methylation levels of the subtelomeric region (D4Z4) and mitochondrial genome (MT-RNR1, D-loop) showed concordance between cord blood and placenta, suggesting a common epigenetic signature of these targets between tissues. Concordance was lacking between the other genes that were studied. In placental tissue, methylation patterns of most targets on the mitochondrial-telomere axis were not strongly influenced by sample location.

journal_name

Placenta

journal_title

Placenta

authors

Janssen BG,Byun HM,Cox B,Gyselaers W,Izzi B,Baccarelli AA,Nawrot TS

doi

10.1016/j.placenta.2014.06.371

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

665-72

issue

9

eissn

0143-4004

issn

1532-3102

pii

S0143-4004(14)00597-9

journal_volume

35

pub_type

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