Genome-wide screen of DNA methylation identifies novel markers in childhood obesity
Genome-wide screen of DNA methylation identifies novel markers in childhood obesity
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DOI：
10.1016/j.gene.2015.04.032
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发表时间：
2015-07-15
期刊：
影响因子：
3.5
通讯作者：
Qi, Kemin
中科院分区：
文献类型：
--
作者：
Ding, Xu;Zheng, Dongyi;Qi, Kemin
表观遗传修饰在慢性非传染性疾病中得到强调。本研究的目的是调查全基因组DNA甲基化，以确定肥胖的甲基化标志物。我们对中国学龄前肥胖儿童的基因启动子和CpG岛进行了全面的DNA甲基化分析，使用甲基化DNA免疫沉淀法确定差异甲基化基因，然后与NimbleGen人类DNA甲基化385K启动子加CpG岛微阵列杂交。结果发现，与瘦型儿童相比，肥胖儿童中有251个启动子和575个CGIs发生了去甲基化，有141个启动子和277个CGIs发生了高甲基化，并且它们在染色体上的分布是不平衡的，在3、16、17和19号染色体上有更多的启动子和CGIs发生了去甲基化，而在X染色体上有更多的差异甲基化启动子和CGIs发生在Y染色体上。进一步分析表明异常甲基化主要发生在HCP启动子和启动子CGIs。在前80个启动子和CGIs中，有肥胖和瘦儿童之间的差异甲基化，近一半是以前研究过的，几乎所有这些都参与了与许多器官相关的癌症的发病机制。此外，验证了具有差异启动子甲基化的四个基因（FZD 7，PRLHR，EXOSC 4和EIF 6），并且必须澄清它们与肥胖的关联。总之，本研究是首次确定中国肥胖儿童甲基化标志物的努力，这对于确定有助于阐明肥胖发病机制及其并发症的标志物具有潜在意义。(C)2015 Elsevier B.V.版权所有。
Epigenetic modifications have been highlighted in chronic non-communicable diseases. The aim of this study was to investigate genome-wide DNA methylation for the identification of methylation markers in obesity. With obese Chinese preschool children, we performed comprehensive DNA methylation profiling of gene promoters and CpG islands to determine the differentially methylated genes using methylated DNA immunoprecipitation followed by hybridization to the NimbleGen Human DNA Methylation 385K Promoter Plus CpG Island Microarray. We found that compared to lean children, 251 promoters and 575 CGIs were demethylated, and 141 promoters and 277 CGIs were hypermethylated in obese children, and their distribution on chromosomes was imbalanced, showing more promoters and CGIs with demethylation on chromosomes 3, 16, 17 and 19 and more differentially methylated promoters and CGIs on chromosome X compared with chromosome Y. Further analysis indicated that aberrant methylations occurred mostly in HCP promoters and promoter CGIs. Among the top 80 promoters and CGIs that had differentiated methylation between obese and lean children, nearly half have been previously studied, and almost all of them are involved in the pathogenesis of cancers that are associated with many organs. Furthermore, four genes (FZD7, PRLHR, EXOSC4, and EIF6) with differential promoter methylation were validated, and their associations with obesity must be clarified. In conclusion, this study represents the first effort to determine methylation markers in obese Chinese children, which has potential relevance for identifying markers that are useful in elucidating the mechanisms of obesity pathogenesis and its complications. (C) 2015 Elsevier B.V. All rights reserved.