Investigation of Gene Expression and DNA Methylation From Seven Different Brain Regions of a Crab-Eating Monkey as Determined by RNA-Seq and Whole-Genome Bisulfite Sequencing

Won-Jun Lim; Kyoung Hyoun Kim; Jae-Yoon Kim; Hee-Jin Kim; Mirang Kim; Jong-Lyul Park; Seokjoo Yoon; Jung-Hwa Oh; Jae-Woo Cho; Yong Sung Kim; Namshin Kim

doi:10.3389/fgene.2019.00694

Investigation of Gene Expression and DNA Methylation From Seven Different Brain Regions of a Crab-Eating Monkey as Determined by RNA-Seq and Whole-Genome Bisulfite Sequencing

Front Genet. 2019 Jul 26:10:694. doi: 10.3389/fgene.2019.00694. eCollection 2019.

Authors

Won-Jun Lim^{1

2}, Kyoung Hyoun Kim^{1

2}, Jae-Yoon Kim^{1

2}, Hee-Jin Kim¹, Mirang Kim¹, Jong-Lyul Park¹, Seokjoo Yoon³, Jung-Hwa Oh³, Jae-Woo Cho³, Yong Sung Kim¹, Namshin Kim^{1

2}

Affiliations

¹ Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea.
² Department of Bioinformatics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon, South Korea.
³ Predictive Toxicity Department, Korea Institute of Toxicology (KIT), Daejeon, South Korea.

Abstract

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 (SLC2A5, MCM5, DRAM1, TTC12, DHX40, COR01A, LRAT, FLVCR2, and PTER) had effects on brain and eye function and development, and two (LHX6 and MEST) 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.

Keywords: Macaca fascicularis; RNA-Seq (quantification) analysis; differentially methylated CpG sites; repeat elements; whole genome bisulfite sequencing (WGBS).