Lim Won-Jun, Kim Kyoung Hyoun, Kim Jae-Yoon, Kim Hee-Jin, Kim Mirang, Park Jong-Lyul, Yoon Seokjoo, Oh Jung-Hwa, Cho Jae-Woo, Kim Yong Sung, Kim Namshin
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea.
Department of Bioinformatics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon, South Korea.
Front Genet. 2019 Jul 26;10:694. doi: 10.3389/fgene.2019.00694. eCollection 2019.
The crab-eating monkey is widely used in biomedical research for pharmacological experiments. Epigenetic regulation in the brain regions of primates involves complex patterns of DNA methylation. Previous studies of methylated CpG-binding domains using microarray technology or peak identification of sequence reads mostly focused on developmental stages or disease, rather than normal brains. To identify correlations between gene expression and DNA methylation levels that may be related to transcriptional regulation, we generated RNA-seq and whole-genome bisulfite sequencing data from seven different brain regions from a single crab-eating monkey. We identified 92 genes whose expression levels were significantly correlated, positively or negatively, with DNA methylation levels. Among them, 11 genes exhibited brain region-specific characteristics, and their expression patterns were strongly correlated with DNA methylation level. Nine genes (, , , , , , , , and ) had effects on brain and eye function and development, and two ( and ) were previously identified as genes in which DNA methylation levels change significantly in the promoter region and are therefore considered brain epigenetic markers. Furthermore, we characterized DNA methylation of repetitive elements at the whole genome through repeat annotation at single-base resolution. Our results reveal the diverse roles of DNA methylation at single-base resolution throughout the genome and reflect the epigenetic variations in adult brain tissues.
食蟹猴在生物医学研究中被广泛用于药理实验。灵长类动物大脑区域的表观遗传调控涉及复杂的DNA甲基化模式。以往使用微阵列技术或序列读取峰识别对甲基化CpG结合域的研究大多集中在发育阶段或疾病，而非正常大脑。为了确定可能与转录调控相关的基因表达与DNA甲基化水平之间的相关性，我们从一只食蟹猴的七个不同脑区生成了RNA测序和全基因组亚硫酸氢盐测序数据。我们鉴定出92个基因，其表达水平与DNA甲基化水平呈显著正相关或负相关。其中，11个基因表现出脑区特异性特征，其表达模式与DNA甲基化水平密切相关。9个基因（，，，，，，，，和）对大脑和眼睛的功能及发育有影响，2个基因（和）先前被鉴定为启动子区域DNA甲基化水平显著变化的基因，因此被视为脑表观遗传标记。此外，我们通过单碱基分辨率的重复注释对全基因组重复元件的DNA甲基化进行了表征。我们的结果揭示了全基因组单碱基分辨率下DNA甲基化的多种作用，并反映了成体脑组织中的表观遗传变异。
