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.

基因体DNA甲基化对基因调控的影响仍然存在很大争议。在本研究中，我们在诱导多能干细胞 (iPSC) 和神经元祖细胞 (NPC) 中生成了具有高测序深度的全基因组亚硫酸氢盐测序 (WGBS) 数据，并研究了 CpG 岛 (CGI) 中 DNA 甲基化变化与相应的关系。 NPC 分化过程中的基因表达。有趣的是，与启动子相比，基因内区域的差异甲基化 CGIs 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甲基化和非甲基化 CGI 的基因表达水平时，与启动子 CGI (pCGI) 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 iCGI 中执行基序搜索，发现 NEUROD1 作为高甲基化 iCGI 结合转录因子。该研究强调了在 iCGI 中激活高甲基化作用的可能性以及与神经元发育相关的 TF 的参与。