Analysis of transcriptional regulation in Treg cells by Id-protein

• Project/Area Number: 15H06330
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Miyazaki Kazuko 京都大学, ウイルス・再生医科学研究所, 特定研究員 (00311811)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 転写制御

Outline of Final Research Achievements

We previously demonstrated the importance of transcriptional regulation by Id2 and Id3 in the immune suppression by regulatory T cell (Treg). Treg cell-specific deletion of Id2 and Id3 results in the spontaneous systemic Th2 inflammation, which closely resemble human allergic disease such as atopic dermatitis and bronchial asthma. To clarify the transcriptional regulation in Treg cell by Id-protein, we performed ATAC-seq analysis using Id-deficient Treg cells. We found the significant changes in chromatin accessibilities in regulatory regions in Id-deficient Treg cells, compared to wild-type Treg cells. A motif analysis for de novo open chromatin regions in enhancers showed E-box motif, which is supposed E2A binding. Together with the E2A ChIP-seq data, we suggest that Id-proteins antagonize E2A enhancer activity in regulatory regions of gene loci of effector molecules such as Cxcr5, Ctla4, and Il-10 to suppress the terminal differentiation of Treg cells.

Research Products

• [Int'l Joint Research] University of California, San Diego/Baylor Institute for Immunology Research(米国)
• [Int'l Joint Research] University of California, San Diego/Baylor Institute for Immunology Research(米国)
• [Journal Article] The E-Id Protein Axis Specifies the Innate and Adaptive Lymphoid Branches of the Immune System (2017)
  • Author(s): Masaki Miyazaki, Kazuko Miyazaki, Kenian Chen, Yi Jin, Jacob Turner, Amanda J. Moore, Rintaro Saito, Kenichi Yoshida, Seishi Ogawa, Hans-Reimer Rodewald, Yin C Lin, Hiroshi Kawamoto and Cornelis Murre
  • Journal Title: Immunity Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant