Rbm10 regulates inflammation development via alternative splicing of Dnmt3b, a DNA methyltransferase

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460574
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Hokkaido University
• Principal Investigator: Atsumi Toru 北海道大学, 遺伝子病制御研究所, 特任助教 (80360478)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 炎症 / DNAメチル化 / 選択的スプライシング

Outline of Final Research Achievements

We previously discovered an inflammation induction mechanism in non-immune cells, the inflammation amplifier. Rbm10 deficiency suppressed NFκB-mediated chemokine and cytokine expression in vitro and inhibited an NFκB-dependent arthritis in vivo.
In Rbm10-deficient cells, NFκB reporter activity was suppressed, and p65 and p300 accumulation at the promoter sites of NFκB-responsive genes was decreased. Epigenetic alterations, including H3K9 acetylation, were also suppressed in contrast, DNA methylation is increased. Rbm10 increasing DNA methylation due to increase enzymatically active Dnmt3b2 and decrease enzymatically inactive Dnmt3b3. These two isoforms, thus increasing DNA methylation. Dnmt3b2 efficient associated with NFκB to methylate modulate the frequency of methylation in the promoter regions of NFκB targets such as inflammatory cytokines and chemokines. These results reveal a novel role of Rbm10 on inflammation development

Free Research Field

免疫学