Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation.
Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation.
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DOI：
10.1371/journal.pone.0186115
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Myatt L
中科院分区：
文献类型：
--
作者：
Mitsuya K;Parker AN;Liu L;Ruan J;Vissers MCM;Myatt L
孕妇肥胖引起的炎症和代谢紊乱会产生不利的宫内环境，增加妊娠并发症和不良胎儿结局，并导致胎儿在以后的生活中出现肥胖和代谢综合征。我们假设胎盘中的表观遗传修饰（包括改变 DNA 甲基化/羟甲基化）可能介导这些效应。从瘦（孕前BMI<25）或肥胖（BMI>30）女性剖腹产后收集足月胎盘绒毛组织。分离基因组 DNA，进行甲基化和羟甲基化 DNA 免疫沉淀，并与 NimbleGen 2.1M 人类 DNA 甲基化阵列杂交。通过 HPLC-ESI-MS 测量胎盘组织中的中间代谢物，通过反相 HPLC 测量抗坏血酸水平，并通过 RT-PCR 测量基因表达。整个基因组中存在差异性甲基化和羟甲基化区域，肥胖组与瘦组相比，甲基化区域增加了 21%，但羟甲基化区域减少了 31%。虽然在 17 号和 19 号染色体上的 GH/CSH 和 PSG 基因簇中多个基因的转录起始位点周围甲基化明显增加和甲基化减少，但在其他区域则没有相关性。仅这些簇中某些基因的甲基化增加与表达减少相关。生物通路分析显示，262 个表现出相互差异甲基化/羟甲基化的基因在妊娠、免疫反应和细胞粘附相关过程中得到富集。我们发现，母亲 BMI 呈负相关，但抗坏血酸与 α-酮戊二酸（一种调节介导 DNA 甲基化的 111 转位酶 (TET)）的代谢物呈正相关。我们提供的证据表明，肥胖母亲的代谢环境与 DNA 甲基化组的改变有关，而 DNA 甲基化组的改变可能会影响与不良后果相关的胎盘基因表达。
The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later life. We hypothesized that epigenetic modifications in placenta including altered DNA methylation/hydroxymethylation may mediate these effects. Term placental villous tissue was collected following cesarean section from lean (prepregnancy BMI<25) or obese (BMI>30) women. Genomic DNA was isolated, methylated and hydroxymethylated DNA immunoprecipitated and hybridized to the NimbleGen 2.1M human DNA methylation array. Intermediate metabolites in placental tissues were measured by HPLC-ESI-MS, ascorbate levels by reverse phase HPLC and gene expression by RT-PCR. Differentially methylated and hydroxymethylated regions occurred across the genome, with a 21% increase in methylated but a 31% decrease in hydroxymethylated regions in obese vs lean groups. Whereas increased methylation and decreased methylation was evident around transcription start sites of multiple genes in the GH/CSH and PSG gene clusters on chromosomes 17 and 19 in other areas there was no relationship. Increased methylation was associated with decreased expression only for some genes in these clusters. Biological pathway analysis revealed the 262 genes which showed reciprocal differential methylation/ hydroxymethylation were enriched for pregnancy, immune response and cell adhesion-linked processes. We found a negative relationship for maternal BMI but a positive relationship for ascorbate with α-ketoglutarate a metabolite that regulates ten eleven translocase (TET) which mediates DNA methylation. We provide evidence for the obese maternal metabolic milieu being linked to an altered DNA methylome that may affect placental gene expression in relation to adverse outcomes.
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与关键基因调节和转录途径相关的新型DNA甲基化谱在生长限制的新生儿的血液和胎盘中。
影响因子：
3.7
作者：
Hillman SL;Finer S;Smart MC;Mathews C;Lowe R;Rakyan VK;Hitman GA;Williams DJ
通讯作者：
Williams DJ
影响因子：
3.7
作者：
Martin E;Ray PD;Smeester L;Grace MR;Boggess K;Fry RC
通讯作者：
Fry RC
表观遗传学的代谢调节。
影响因子：
29
作者：
Lu C;Thompson CB
通讯作者：
Thompson CB
DOI：
10.1016/j.tig.2014.07.005
发表时间：
2014-10
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Huang Y;Rao A
通讯作者：
Rao A
影响因子：
3.7
作者：
Chia, Nancy;Wang, Luan;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.