Cytosine methylation dysregulation in neonates following intrauterine growth restriction.
Cytosine methylation dysregulation in neonates following intrauterine growth restriction.
复制标题
宫内生长限制后，新生儿的胞嘧啶甲基化失调。
DOI：
10.1371/journal.pone.0008887
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发表时间：
2010-01-26
期刊：
影响因子：
3.7
通讯作者：
Greally JM
中科院分区：
文献类型：
--
作者：
Einstein F;Thompson RF;Bhagat TD;Fazzari MJ;Verma A;Barzilai N;Greally JM
子宫内环境的扰动会影响胎儿在可塑性关键时期的发育，并会增加对许多年龄相关疾病的易感性（例如，2型糖尿病; T2 DM），晚至数十年后才出现。我们假设这种生物记忆是由干细胞群体中表观基因组的永久性改变介导的，并将我们的研究专门集中在来自宫内生长受限（IUGR）新生儿和对照受试者的脐带血中的CD 34+造血干细胞和祖细胞中的DNA甲基化。我们的表观基因组检测采用了两阶段设计，涉及全基因组发现，然后是定量的单位点验证。我们发现，胞嘧啶甲基化的变化发生在对中度IUGR的反应中，涉及有限数量的位点。我们还确定了DNA甲基化失调的特定基因座，特别是肝细胞核因子4α（HNF 4A）基因，一个众所周知的糖尿病候选基因，以前与子宫内生长受限无关，以及其他编码HNF 4A相互作用蛋白的基因座。我们的研究结果提供了深入了解表观基因组失调在介导IUGR的长期后果中的潜在贡献，并证明了这种方法对成人疾病的胎儿起源研究的价值。
Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.
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影响因子：
78.5
作者：
Issa, JP
通讯作者：
Issa, JP
DOI：
10.1080/07315724.2004.10719428
发表时间：
2004-12-01
影响因子：
3.5
作者：
Barker, DJP
通讯作者：
Barker, DJP
影响因子：
7
作者：
Khulan, Batbayar;Thompson, Reid F.;Greally, John M.
通讯作者：
Greally, John M.
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M
影响因子：
7.7
作者：
Boloker, J;Gertz, SJ;Simmons, RA
通讯作者：
Simmons, RA