Previous studies have generated controversial findings regarding the correlation between DNA methylation in the human genome and gene expression. Some reports have indicated that promoter methylation is negatively correlated with gene expression levels; however, in some cases, a poor or positive correlation was reported. Most previous findings were based on general trends observed with whole-genome data analysis. Here, we present a novel chromosome-specific statistical analysis design of empirical Bayes differential tests for five phases of erythroid development. To better understand the common methylation patterns of differentially methylated regions (DMRs) during specific stages, we defined differential phases for each CpG locus, based on a maximum log2 fold change. Analyzing hypermethylated and hypomethylated CpG loci separately showed variations in methylation patterns during erythropoiesis in the gene body, promoter and enhancer regions. Hypomethylated DMRs showed stronger associations with erythroid-specific enhancers at the differentiation start phase and with exons in the intermediate phase. To investigate the hypomethylated DMRs further, transcription factor binding site-enrichment analysis was conducted. This analysis highlighted novel transcription factors during each differentiation stage that were not detected by previous differential methylation data analysis. In contrast, hypermethylated DMRs showed a consistent methylation pattern over the different genomic regions. Thus, a closer examination of DNA methylation patterns in a single chromosome during each developmental stage can contribute to verify the association nature between gene expression and DNA methylation.

中文翻译：

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人类红细胞生成在16号染色体上的阶段特异性DNA甲基化差异数据分析

先前的研究产生了关于人类基因组中的DNA甲基化与基因表达之间的相关性的有争议的发现。一些报道表明，启动子甲基化与基因表达水平负相关。但是，在某些情况下，据报道相关性很差或正。先前的大多数发现是基于全基因组数据分析观察到的总体趋势。在这里，我们提出了经验性贝叶斯差异测试针对红系发育五个阶段的新型染色体特定统计分析设计。为了更好地理解特定阶段差异甲基化区域（DMR）的常见甲基化模式，我们基于最大log2倍数变化定义了每个CpG基因座的差异相。分别分析高甲基化和低甲基化的CpG基因座显示在基因体，启动子和增强子区域的红细胞生成过程中甲基化模式的变化。次甲基化DMRs在分化开始阶段与红系特异增强子和在中间阶段与外显子有更强的联系。为了进一步研究低甲基化的DMR，进行了转录因子结合位点富集分析。该分析突出显示了每个分化阶段的新转录因子，以前的差异甲基化数据分析未检测到这些转录因子。相反，高甲基化DMR在不同基因组区域显示出一致的甲基化模式。从而，