Regulation of the activity of IFN-gamma promoter elements during Th cell differentiation
| Autor: | F, Zhang, D Z, Wang, M, Boothby, L, Penix, R A, Flavell, T M, Aune |
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| Rok vydání: | 1998 |
| Předmět: |
Down-Regulation
Nuclear Proteins Cell Differentiation Mice Transgenic T-Lymphocytes Helper-Inducer Regulatory Sequences Nucleic Acid Th1 Cells Binding Competitive Interleukin-12 Mice Inbred C57BL Transcription Factor AP-1 Interferon-gamma Mice Mice Inbred CBA Animals Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Cells Cultured Protein Binding |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 161(11) |
| ISSN: | 0022-1767 |
| Popis: | Before they can deliver their effector functions, CD4+ Th cells must differentiate into Th1 or Th2 subsets. We have prepared reporter transgenic mice that express the luciferase gene under the control of proximal (prox.IFN-gamma) and distal (dist.IFN-gamma) regulatory elements from the IFN-gamma promoter to permit investigation of mechanisms that regulate IFN-gamma gene transcription during Th cell differentiation. Precursor Th cells (pTh) contain high levels of cAMP response element binding protein-activation transcription factor-1 (CREB-ATF1) proteins that bind these promoter elements from the IFN-gamma gene, and these cells fail to express promoter activity. Restimulated effector Th (eTh) cells have reduced levels of CREB-ATF1 proteins, their nuclear extracts exhibit reduced CREB-ATF1 binding and greater Jun and Jun-ATF2 binding to dist.IFN-gamma), and eTh cells express promoter activity. CREB directly competes with effector T cell nuclear proteins for dist.IFN-gamma binding, and overexpression of CREB inhibits both prox.IFN-gamma- and dist.IFN-gamma-directed transcription in Jurkat T cells. IL-12-stimulated Thl differentiation increases dist.IFN-gamma activity in restimulated eTh1 cells; eTh1 nuclear extracts form increased levels of Jun-ATF2-dist.IFN-gamma complexes. Taken together, these data suggest that both de-repression and trans-activation contribute to the induction of IFN-gamma gene transcription during Th1 differentiation. |
| Databáze: | OpenAIRE |
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