DNA Methylation-dependent regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19601
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Okayama University
• Principal Investigator: MIYAWAKI Yoshia 岡山大学, 医歯薬学総合研究科, 非常勤研究員 (10761116)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: SLE / Ctse / Kaiso / Epigenetics / DNA methylation / CD4陽性T細胞

Outline of Final Research Achievements

Global DNA hypomethylation in T cells in systemic lupus erythematosus (SLE) patients was involved in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and the transcript level was upregulated in MRL compared with B6. Among them, we focused on a mCGCG which was hypomethylated and mutated to CGGG in MRL. The binding of Kaiso, a repressive transcriptional factor recognized mCGmCG motif was reduced in MRL and EL4 cells treated with 5-azaC and/or Trichostatin A. In addition, IL-10 secretion was reduced in EL4 cells transfected with siCtse. In conclusion, reduced recruitment of Kaiso to the hypometylated mCGCG motif induced the overexpression of Ctse and IL-10 in CD4+ cells which may be involved in the pathogenesis of SLE.

Free Research Field

リウマチ膠原病学