Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta.
Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta.
复制标题
在脐带血和胎盘中线粒体 - 凝结仪轴上与年龄相关靶标的DNA甲基化的变化。
DOI：
10.1016/j.placenta.2014.06.371
复制
发表时间：
2014-09
期刊：
影响因子：
3.8
通讯作者：
Nawrot TS
中科院分区：
文献类型：
--
作者：
Janssen BG;Byun HM;Cox B;Gyselaers W;Izzi B;Baccarelli AA;Nawrot TS
表观遗传学是组织特异性的，甚至可能是细胞特异性的，但人类生殖研究中关于脐带血和胎盘中DNA甲基化模式的一致性以及胎盘内变异的信息很少。我们评估了生物衰老途径中候选基因（SIRT 1，TP 53，PPARG，PPARGC 1A和TFAM）启动子区，亚端粒区（D4 Z4）和线粒体基因组（MT-RNR 1，D-loop）的甲基化水平。从ENVIRONAGE出生队列中随机选择90名个体，使用高度定量的亚硫酸氢盐-PCR焦磷酸测序来评估脐带血和胎盘之间的甲基化一致性。在一个19人的子集中，进行了更广泛的抽样方案，以检查胎盘内的变化。脐带血和胎盘组织端粒下区和线粒体基因组DNA甲基化水平一致，相关系数范围为r = 0.31至0.43，p ≤ 0.005，母体和胎儿胎盘组织之间也一致（r = 0.53至0.72，p ≤ 0.05）。对于大多数靶点，发现四个胎儿活检之间的甲基化水平一致（组内相关系数范围为0.16至0.72），表明胎盘内变异较小。亚端粒区（D4 Z4）和线粒体基因组（MT-RNR 1，D-loop）的甲基化水平在脐带血和胎盘之间显示出一致性，表明这些靶点在组织之间具有共同的表观遗传特征。其他被研究的基因之间缺乏一致性。在胎盘组织中，大多数靶点在胎盘-端粒轴上的甲基化模式不受样品位置的强烈影响。
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). 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. 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. 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.