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Role of DNA methylation on human CTSG in dermatomyositic myoideum
Author(s) -
Peng Yue,
Sun Xiaofeng,
Liang Ying
Publication year - 2020
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11447
Subject(s) - dna methylation , microbiology and biotechnology , biology , methylation , epigenetics , chromatin immunoprecipitation , cancer research , dnmt3b , methylated dna immunoprecipitation , promoter , dna , genetics , gene , gene expression
Dermatomyositis (DM) is a multifactorial chronic autoimmune disorder with characteristic skin and muscle pathological changes and involvement of other organ systems. Cathepsin G (CTSG) contributes to the risk of developing DM, which is likely to be associated with inflammatory cytokines. Differential DNA methylation on CTSG has been determined to be implicated in DM in vivo. However, the underlying mechanism of this epigenetic regulation on CTST in DM is poorly explored. In this study, we investigated DNA methylation signature on CTSG at single‐nucleotide resolution in quadriceps femoris of six DM patients and paracancerous muscles of three patients with rhabdomyosarcoma on inner thigh using pyrosequencing and observed that the overall DNA methylation level of CTSG was increased in DM compared with control, in which CpG loci at third and fourth exons but not promoter contributed to the significant hypermethylation. Furthermore, we observed that transcription and DNA methylation of CTSG were both declined in DNMT3a knockdown compared with DNMT1 and DNMT3b knockdown in human skeletal muscle SJCRH30 and A‐204 cell lines exposed to tumor necrosis factor‐α. Furthermore, Bortezomib (NF‐κB inhibitor) and Brevilin A (JAK/STAT inhibitor) were employed to treat SJCRH30 and A‐204 cells, respectively, and we observed that CTSG was hypomethylated and silenced after Bortezomib treatment compared with untreatment and Brevilin A. Finally, chromatin immunoprecipitation‐quantitative polymerase chain reaction indicated that DNMT3a could bind to the coding regions of CTSG and the interaction was dependent on NF‐κB activity. Taken together, our results determined a novel regulatory mechanism of DNA methylation on CTSG in DM.