Aberrant gene transcription based on chromatin structure in rheumatoid arthritis synovial fibroblasts

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09903
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Saitama Medical University
• Principal Investigator: Araki Yasuto 埼玉医科大学, 医学部, 講師 (10580839)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 関節リウマチ / エピジェネティクス / クロマチン / ヒストンメチル化 / 転写因子

Outline of Final Research Achievements

Rheumatoid arthritis (RA) is a disease in which the etiology is unknown and the treatment is difficult. To elucidate epigenetic dysregulation in RA, we examined the mechanisms of aberrant gene transcription based on the interaction of chromatin structure and transcription factors (TFs) in RA synovial fibroblasts (SFs). We analyzed chromatin structure by investigating histone modifications with ChIP-seq in RASFs. We examined open chromatin regions that regulate gene transcription by FAIRE-seq. We identified SOX11 as a RASF-specific TF by analyzing TF consensus motifs of the regions.

Free Research Field

リウマチ・膠原病

Academic Significance and Societal Importance of the Research Achievements

関節リウマチ（RA）特異的な転写因子としてSOX11を同定したが、SOX11はRA線維芽細胞（SF）の活性化に必要な事が示唆される。つまり、SOX11を標的とした治療を行う事によりSOX11の機能を低下させる事ができれば、RASFsの活性化を抑制する事が期待される。このように、今回の結果は新規のRA治療につながる重要なものである。