A novel approach identifies new differentially methylated regions (DMRs) associated with imprinted genes
A novel approach identifies new differentially methylated regions (DMRs) associated with imprinted genes
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DOI：
10.1101/gr.111922.110
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发表时间：
2011-03-01
期刊：
影响因子：
7
通讯作者：
Weksberg, Rosanna
中科院分区：
文献类型：
--
作者：
Choufani, Sanaa;Shapiro, Jonathan S.;Weksberg, Rosanna
印迹基因对人类正常生长和神经发育至关重要。它们的特点是DNA的差异甲基化区域（DMRs）赋予亲本起源特异性转录。我们开发了一种新的策略来识别与印迹基因相关的dmr。利用亚硫酸氢钠修饰的双亲本正常人组织DNA的全基因组甲基化分析，通过选择甲基化水平与假定的等位基因差异甲基化一致的CpGs来鉴定候选DMRs。与此同时，研究人员检测了单亲本来源的组织，即父本来源的雄性激素源性完全包子痣（AnCHMs）和母本来源的成熟卵巢囊性畸胎瘤（MCT）的甲基化谱，然后用于鉴定具有亲本来源特异性DNA甲基化的CpGs。通过这种方法，我们发现了与印迹基因组区域相关的已知DMRs，以及已知印迹基因NAP1L5和ZNF597的新DMRs，以及新的候选印迹基因。其中一个候选基因AXL（一种酪氨酸激酶受体）的父本甲基化DMR也在小鼠胚胎实验中得到验证，表明AXL以DNA甲基化依赖的方式优先从母体等位基因表达。
Imprinted genes are critical for normal human growth and neurodevelopment. They are characterized by differentially methylated regions (DMRs) of DNA that confer parent of origin-specific transcription. We developed a new strategy to identify imprinted gene-associated DMRs. Using genome-wide methylation profiling of sodium bisulfite modified DNA from normal human tissues of biparental origin, candidate DMRs were identified by selecting CpGs with methylation levels consistent with putative allelic differential methylation. In parallel, the methylation profiles of tissues of uniparental origin, i.e., paternally-derived androgenetic complete hydatidiform moles (AnCHMs), and maternally-derived mature cystic ovarian teratoma (MCT), were examined and then used to identify CpGs with parent of origin-specific DNA methylation. With this approach, we found known DMRs associated with imprinted genomic regions as well as new DMRs for known imprinted genes, NAP1L5 and ZNF597, and novel candidate imprinted genes. The paternally methylated DMR for one candidate, AXL, a receptor tyrosine kinase, was also validated in experiments with mouse embryos that demonstrated Axl was expressed preferentially from the maternal allele in a DNA methylation-dependent manner.