DNA Methylation of Intragenic CpG Islands are Required for Differentiation from iPSC to NPC
DNA Methylation of Intragenic CpG Islands are Required for Differentiation from iPSC to NPC
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DOI：
10.1007/s12015-020-10041-6
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发表时间：
2020-09-25
影响因子：
4.8
通讯作者：
Kim, Young-Joon
中科院分区：
文献类型：
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作者：
Choi, Won-Young;Hwang, Ji-Hyun;Kim, Young-Joon
基因体DNA甲基化对基因调控的影响仍然存在很大争议。本研究通过对诱导多能干细胞（iPSC）和神经元祖细胞（NPC）的全基因组亚硫酸氢盐测序（WGBS），探讨了NPC分化过程中CpG岛（CGIs）DNA甲基化变化与相应基因表达的关系。有趣的是，与启动子相比，差异甲基化的基因内CGIs在基因内区域中更丰富，并且这些甲基化的基因内CGIs（iCGIs）与神经元发育相关基因相关。当我们比较基因内区域的甲基化和非甲基化CGIs的基因表达水平时，与启动子CGIs（pCGIs）相比，iCGI的DNA甲基化与基因表达呈正相关。为了深入了解iCGI DNA甲基化介导的调控机制，我们在高甲基化的iCGI中进行了基序搜索，发现NEUROD1是一个高甲基化的iCGI结合转录因子。这项研究强调了iCGIs中高甲基化激活作用的可能性，并涉及神经元发育相关的TF。
The effects of gene body DNA methylation on gene regulation still remains highly controversial. In this study, we generated whole genome bisulfite sequencing (WGBS) data with high sequencing depth in induced pluripotent stem cell (iPSC) and neuronal progentior cell (NPC), and investigated the relationship between DNA methylation changes in CpG islands (CGIs) and corresponding gene expression during NPC differentiation. Interestingly, differentially methylated CGIs were more abundant in intragenic regions compared to promoters and these methylated intragenic CGIs (iCGIs) were associated with neuronal development-related genes. When we compared gene expression level of methylated and unmethylated CGIs in intragenic regions, DNA methylation of iCGI was positively correlated with gene expression in contrast with promoter CGIs (pCGIs). To gain insight into regulatory mechanism mediated by iCGI DNA methylation, we executed motif searching in hypermethylated iCGIs and found NEUROD1 as a hypermethylated iCGI binding transcription factor. This study highlights give rise to possibility of activating role of hypermethylation in iCGIs and involvement of neuronal development related TFs.