PU.1 is required for transcriptional activation of the Stat6 response element in the Igε promoter
| Autor: | Marko Pesu, Tuuli Välineva, Olli Silvennoinen, Saara Aittomäki |
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| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
Carcinoma Hepatocellular Immunology Response element CAAT box E-box Biology Transfection Transactivation Genes Reporter Proto-Oncogene Proteins Protein Interaction Mapping Tumor Cells Cultured Humans Point Mutation Immunology and Allergy Promoter Regions Genetic Enhancer Hormone response element Binding Sites Genes Immunoglobulin integumentary system General transcription factor Liver Neoplasms Promoter Immunoglobulin E respiratory system Burkitt Lymphoma Molecular biology Protein Structure Tertiary Gene Expression Regulation Trans-Activators Interleukin-4 STAT6 Transcription Factor Protein Binding |
| Zdroj: | European Journal of Immunology. 33:1727-1735 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200323680 |
| Popis: | Signal transducer and activator of transcription 6 (Stat6) has a crucial role in regulation of IL-4-induced gene responses. Stat6-binding sites are present in the promoters of both ubiquitously and cell-type-specifically expressed genes. The promoter regions of IL-4-inducible genes contain cis-acting elements for several transcription factors that act in concert with Stat6 and are also likely to modulate lineage-specific gene expression. We have observed that the Stat6 response element from the B-cell-specific Igepsilon promoter is readily activated upon IL-4 stimulation in B cells but not in non-hematopoietic cells. A minimal low-affinity PU.1-core-binding sequence (5'-AGAA-3') was identified within the Stat6 DNA-binding site in the Igepsilon promoter. Ectopic expression of the myeloid- and B-cell-specific transcription factor PU.1 restored the IL-4-inducibility of the Igepsilon-Stat6 response element in HepG2 cells, and the induction required an intact PU.1-binding sequence. Both the transactivation and the DNA-binding domains of PU.1 were required for induction of Stat6-mediated transcription. The co-operation between PU.1 and Stat6 in transactivation of the Igepsilon gene represents a molecular mechanism for the fine-tuning of cell-type-restricted expression of IL-4-induced gene responses. |
| Databáze: | OpenAIRE |
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