Structural and regulatory characterization of the placental epigenome at its maternal interface.
Structural and regulatory characterization of the placental epigenome at its maternal interface.
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DOI：
10.1371/journal.pone.0014723
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发表时间：
2011-02-23
期刊：
影响因子：
3.7
通讯作者：
Peters DG
中科院分区：
文献类型：
--
作者：
Chu T;Handley D;Bunce K;Surti U;Hogge WA;Peters DG
表观遗传学可以被宽泛地定义为以不依赖于基本的初级DNA序列的方式影响生物表型的细胞“性状”的研究。表观遗传学可能对生物表型产生深远影响的一种情况是在子宫内发育期间。在这种情况下，有一个确定的和关键的窗口，在此期间平衡的稳态是必要的正常胎儿生长和发育。我们已经进行了详细的结构和功能分析的胎盘表观基因组在其母体界面。具体而言，我们使用市售和定制设计的微阵列对绒毛膜绒毛（CVS）和母体血细胞（MBC）样品中的DNA甲基化进行了全基因组分析。然后，我们将这些数据与相同组织的全基因组转录数据进行了比较。除了发现CVS基因组比MBC基因组低甲基化程度更高之外，我们还鉴定了许多组织特异性差异甲基化区域（T-DMR）。我们进一步发现，这些T-DMR在空间上沿着基因组聚集，并且富集了具有组织特异性生物学功能的基因。我们确定了与不同基因组结构（如基因体、启动子和CpG岛）相关的DNA甲基化的独特模式，并分别确定了基因体和启动子中DNA甲基化水平与基因表达水平之间的直接和反向关系。此外，我们发现这些关系与CpG含量显著相关。我们的结论是，早期妊娠胎盘DNA甲基化组是高度组织化的，是显着的和全球性的转录相关。这些数据提供了一个独特的洞察胎盘表观基因组在其母体界面的结构和调控特征，并将推动未来的分析胎盘功能障碍在妊娠期疾病中的作用。
Epigenetics can be loosely defined as the study of cellular “traits” that influence biological phenotype in a fashion that is not dependent on the underlying primary DNA sequence. One setting in which epigenetics is likely to have a profound influence on biological phenotype is during intrauterine development. In this context there is a defined and critical window during which balanced homeostasis is essential for normal fetal growth and development. We have carried out a detailed structural and functional analysis of the placental epigenome at its maternal interface. Specifically, we performed genome wide analysis of DNA methylation in samples of chorionic villus (CVS) and maternal blood cells (MBC) using both commercially available and custom designed microarrays. We then compared these data with genome wide transcription data for the same tissues. In addition to the discovery that CVS genomes are significantly more hypomethylated than their MBC counterparts, we identified numerous tissue-specific differentially methylated regions (T-DMRs). We further discovered that these T-DMRs are clustered spatially along the genome and are enriched for genes with tissue-specific biological functions. We identified unique patterns of DNA methylation associated with distinct genomic structures such as gene bodies, promoters and CpG islands and identified both direct and inverse relationships between DNA methylation levels and gene expression levels in gene bodies and promoters respectively. Furthermore, we found that these relationships were significantly associated with CpG content. We conclude that the early gestational placental DNA methylome is highly organized and is significantly and globally associated with transcription. These data provide a unique insight into the structural and regulatory characteristics of the placental epigenome at its maternal interface and will drive future analyses of the role of placental dysfunction in gestational disease.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
影响因子：
9.3
作者：
Chan, K. C. Allen;Ding, Chunming;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis
影响因子：
9.8
作者：
Rakyan, VK;Hildmann, T;Beck, S
通讯作者：
Beck, S
DOI：
10.1089/gte.2006.10.44
发表时间：
2006-03-01
期刊：
GENETIC TESTING
影响因子：
--
作者：
Iovannisci, DM;Ha, TT;Shaw, GM
通讯作者：
Shaw, GM
影响因子：
11.2
作者：
Bollati, Valentina;Baccarelli, Andrea;Yang, Allen S.
通讯作者：
Yang, Allen S.