title: Aberrant methylation patterns affect the molecular pathogenesis of rheumatoid arthritis.
abstract: This study aims to investigate DNA methylation signatures in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA), and to explore the relationship with transcription factors (TFs) that help to distinguish RA from osteoarthritis (OA). Microarray dataset of GSE46346, including six FLS samples from patients with RA and five FLS samples from patients with OA, was downloaded from the Gene Expression Omnibus database. RA and OA samples were screened for differentially methylated loci (DMLs). The corresponding differentially methylated genes (DMGs) were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis. A transcriptional regulatory network was built with TFs and their corresponding DMGs. Overall, 280 hypomethylated loci and 561 hypermethylated loci were screened. Genes containing hypermethylated loci were enriched in pathways in cancer, ECM-receptor interaction, focal adhesion and neurotrophin signaling pathways. Genes containing hypomethylated loci were enriched in the neurotrophin signaling pathway. Moreover, we found that CCCTC-binding factor (CTCF), Yin Yang 1 (YY1), v-myc avian myelocytomatosis viral oncogene homolog (c-MYC), and early growth response 1 (EGR1) were important TFs in the transcriptional regulatory network. Therefore, DMGs might participate in the neurotrophin signaling pathway, pathways in cancer, ECM-receptor interaction and focal adhesion pathways in RA. Furthermore, CTCF, c-MYC, YY1, and EGR1 may play important roles in RA through regulating DMGs.
authors.affiliation: Department of Orthopedics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jiefang Ave, Wuhan 430030, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jiefang Ave, Wuhan 430030, PR China. Electronic address: zhengqiangLuolzhq@126.com.
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Luo
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics*; D000076246:CCCTC-Binding Factor; D019175:DNA Methylation; D003937:Diagnosis, Differential; D051766:Early Growth Response Protein 1 / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000175:diagnosis / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000070918:Synoviocytes / Q000502:physiology*; D050986:YY1 Transcription Factor / Q000235:genetics
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C489427:MYC protein, human; D009414:Nerve Growth Factors; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human
keywords: DNA methylation; Gene ontology; Pathway; Rheumatoid arthritis; Transcription factor