STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locus
Autor: | Audrey O'Sullivan, Hua Chen Chang, Mark H. Kaplan, Qing Yu |
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Rok vydání: | 2003 |
Předmět: |
musculoskeletal diseases
Histone-modifying enzymes Time Factors Transcription Genetic Cell Separation Biology Biochemistry Models Biological Polymerase Chain Reaction Chromatin remodeling Histones Mice immune system diseases Animals RBBP4 RNA Messenger skin and connective tissue diseases Promoter Regions Genetic Molecular Biology ChIA-PET Regulation of gene expression Mice Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction Cell Membrane Nuclear Proteins hemic and immune systems Receptors Interleukin-2 Cell Biology STAT4 Transcription Factor Blotting Northern Flow Cytometry Molecular biology Mi-2/NuRD complex CREB-Binding Protein Interleukin-12 Precipitin Tests Chromatin DNA-Binding Proteins Trans-Activators Chromatin immunoprecipitation Spleen Protein Binding |
Zdroj: | The Journal of biological chemistry. 279(8) |
ISSN: | 0021-9258 |
Popis: | Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)-stimulated inflammatory immune responses. Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor alpha chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. Thus, these results provide a model for STAT4-dependent gene induction and a mechanism for cytokine-induced expression of the CD25 gene. |
Databáze: | OpenAIRE |
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