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Integrated analysis of genome-wide DNA methylation and gene expression data provide a regulatory network in intrauterine growth restriction

机译：基因组DNA甲基化和基因表达数据的综合分析提供了宫内生长限制的调节网络

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Abstract Intrauterine growth restriction (IUGR), a serious complication of perinatal period, results in metabolic and brain disorders. However, the exact cause of IUGR remains unclear. Recently, some evidences indicated that epigenetic modification plays an important role in IUGR. Hence, in this study the methylation status and gene expression profiles of IUGR were compared to investigate the changes in epigenetic regulation and gene expression induced by IUGR. DNA samples extracted from blood samples of infants with IUGR and controls appropriate for gestational age (AGA) were analyzed with Illumina Human Methylation 450 k array to identify differences in genome-wide DNA methylation, and results were verified by Mass ARRAY. Moreover, an IUGR rat model was established by maternal malnutrition method, and gene expression profiles associated with progressive DNA methylation changes in brain tissue were detected using microarray Affymetrix Rat Gene 2.0ST. Based on DNA methylation array, 2265 genes are differentially methylated between IUGR and AGA 1338 genes in the promoter region. Genes with differentially methylated CpG loci in the promoter region enriched in 10 pathways.1311 differentially expressed genes were obtained by Microarray. 36 significantly enriched pathways were identified. After comparing DNA methylation data with gene expression data, 49 genes showed a negative correlation between DNA methylation and gene expression. 27 commonly enriched pathways were identified, which involved sugar, fat and protein metabolism, diseases of the nervous system, cancer, and immunomodulation and endocrine regulation. These findings suggest the epigenetic regulatory mechanisms on corresponding gene expression which may play a role in the adult-onset diseases induced by IUGR. Highlights ? Investigate the epigenetic modification in IUGR ? Analysis of genome-wide DNA methylation and gene expression with Illumina ? Human Methylation 450 k array and microarray Affymetrix Rat Gene 2.0ST. ? Validation with the MassARRAY Compact system Sequenom
机译：摘要宫内生长限制（IUGR），围产期严重并发症，导致代谢和脑病。然而，IUGR的确切原因仍然不清楚。最近，一些证据表明，表观遗传修改在IUGR中起着重要作用。因此，在该研究中，对IUGR的甲基化状态和基因表达谱进行了比较，以研究IUGR诱导的表观遗传调控和基因表达的变化。用IULMIN人甲基化450k阵列分析从IUGR和适合于妊娠期（AGA）的IUGR和对照的对照中提取的DNA样品，以鉴定基因组DNA甲基化的差异，并通过质量阵列验证结果。此外，使用母体营养素方法建立了IugR大鼠模型，并且使用微阵列无论大鼠2.0st检测与脑组织脑组织中逐步DNA甲基化变化相关的基因表达谱。基于DNA甲基化阵列，2265个基因在启动子区的IUGR和AGA 1338基因之间差异甲基化。通过微阵列获得富含10个途径的启动子区中具有差异甲基化CpG基因座的基因。鉴定了显着富集的途径。在将DNA甲基化数据与基因表达数据进行比较后，49个基因显示DNA甲基化和基因表达之间的负相关。鉴定了27种常见的途径，其中涉及糖，脂肪和蛋白质代谢，神经系统的疾病，癌症和免疫调节和内分泌调节。这些研究结果表明，对应于IUGR诱导的成人发作疾病中可能发挥作用的对应基因表达的表观遗传调节机制。强调 ？调查IUGR中的表观遗传修饰？含Illumina基因组DNA甲基化和基因表达的分析吗？人甲基化450 k阵列和微阵列染色鼠大鼠2.0st。还是使用MassArray紧凑型系统亮片验证

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