標題: Next-Generation Sequencing Profiles of the Methylome and Transcriptome in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis
作者: Tseng, Chia-Chun
Lin, Yuan-Zhao
Lin, Chia-Hui
Li, Ruei-Nian
Yen, Chang-Yi
Chan, Hua-Chen
Tsai, Wen-Chan
Ou, Tsan-Teng
Wu, Cheng-Chin
Sung, Wan-Yu
Yen, Jeng-Hsien
生物科技學系
Department of Biological Science and Technology
關鍵字: rheumatoid arthritis;methylation;next-generation sequencing
公開日期: 1-九月-2019
摘要: Using next-generation sequencing to decipher methylome and transcriptome and underlying molecular mechanisms contributing to rheumatoid arthritis (RA) for improving future therapies, we performed methyl-seq and RNA-seq on peripheral blood mononuclear cells (PBMCs) from RA subjects and normal donors. Principal component analysis and hierarchical clustering revealed distinct methylation signatures in RA with methylation aberrations noted across chromosomes. Methylation alterations varied with CpG features and genic characteristics. Typically, CpG islands and CpG shores were hypermethylated and displayed the greatest methylation variance. Promoters were hypermethylated and enhancers/gene bodies were hypomethylated, with methylation variance associated with expression variance. RA genetically associated genes preferentially displayed differential methylation and differential expression or interacted with differentially methylated and differentially expressed genes. These differentially methylated and differentially expressed genes were enriched with several signaling pathways and disease categories. 10 genes (CD86, RAB20, XAF1, FOLR3, LTBR, KCNH8, DOK7, PDGFA, PITPNM2, CELSR1) with concomitantly differential methylation in enhancers/promoters/gene bodies and differential expression in B cells were validated. This integrated analysis of methylome and transcriptome identified novel epigenetic signatures associated with RA and highlighted the interaction between genetics and epigenetics in RA. These findings help our understanding of the pathogenesis of RA and advance epigenetic studies in regards to the disease.
URI: http://dx.doi.org/10.3390/jcm8091284
http://hdl.handle.net/11536/153125
DOI: 10.3390/jcm8091284
期刊: JOURNAL OF CLINICAL MEDICINE
Volume: 8
Issue: 9
起始頁: 0
結束頁: 0
顯示於類別:期刊論文