DNA methylation subpatterns at distinct regulatory regions in human early embryos

作者：Rongsong Luo, Chunling Bai, Lei Yang, Zhong Zheng, Guanghua Su, Guangqi Gao, Zhuying Wei, Yongchun Zuo, Guangpeng Li · 发表于：Open Biology · 年份：2018 · DOI：10.1098/rsob.180131 · 被引用次数：39 · 研究领域：Epigenetics and DNA Methylation、Genetic Syndromes and Imprinting、Pluripotent Stem Cells Research

DNA methylation has been investigated for many years, but recent technologies have allowed for single-cell- and single-base-resolution DNA methylation datasets and more accurate assessment of DNA methylation dynamics at the key genomic regions that regulate gene expression in human early embryonic development. In this study, the region from upstream 20 kb to downstream 20 kb of RefSeq gene was selected and divided into 12 distinct regions (up20, up10, up5, up2, 5'UTR, exon, intron, 3'UTR, down2, down5, down10 and down20). The candidate promoter region (TSS ± 2 kb) was further divided into 20 consecutive subregions, which were termed 'bins'. The DNA methylation dynamics of these regions were systematically analysed along with their effects on gene expression in human early embryos. The dynamic DNA methylation subpatterns at the distinct genomic regions with a focus on promoter regions were mapped. For the 12 distinct genomic regions, up2 and 5'UTR had the lowest DNA methylation levels, and their methylation dynamics were different with other regions. The region 3'UTR had the highest DNA methylation levels, and the correlation analysis with gene expression proved that it was a feature of transcribed genes. For the 20 bins in promoter region, the CpG densities showed a normal distribution pattern, and the trend of the methylated CpG counts was inverse with the DNA methylation levels, especially for the bin 1 (downstream 200 bp of the TSS). Through the correlation analysis betwee...