Identification of cis-Acting Regulatory Elements Controlling Interleukin-4 Gene Expression in T Cells: Roles for NF-Y and NF-ATc
| Autor: | S J, Szabo, J S, Gold, T L, Murphy, K M, Murphy |
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| Rok vydání: | 1993 |
| Předmět: |
Base Sequence
NFATC Transcription Factors T-Lymphocytes DNA Mutational Analysis Molecular Sequence Data Oligonucleotides Nuclear Proteins Cell Biology In Vitro Techniques DNA-Binding Proteins Mice Gene Expression Regulation Consensus Sequence CCAAT-Enhancer-Binding Proteins Tumor Cells Cultured Animals Interleukin-4 RNA Messenger Promoter Regions Genetic Molecular Biology Sequence Deletion Transcription Factors Research Article |
| Zdroj: | Molecular and Cellular Biology. 13:4793-4805 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.13.8.4793-4805.1993 |
| Popis: | Activity of the murine interleukin-4 (IL-4) promoter was localized to several cis-acting elements present within the first 300 bp from the transcriptional initiation site. Five repeated elements, P0 to P4, that share the common consensus ATTTTCCNNT were located between -40 and -250, and each was shown to interact with the T-cell-specific factor NF(P). These distinct P sites appear functionally interchangeable and cooperatively confer cyclosporin A-sensitive and ionomycin-inducible promoter activity. NF(P) may be closely related to the cytoplasmic component of NF-AT (nuclear factor of activated T cells), a T-cell-specific factor essential for IL-2 gene transcription, as judged from indistinguishable molecular weights and protease fragmentation patterns of UV-photolabeled factors. Also, we identified an element in the IL-4 promoter with homology to the Y box common to all major histocompatibility complex class II gene promoters. Our data show that the IL-4 promoter Y box -114CTGATTGG-107 significantly enhances overall promoter activity, since point mutations within this element diminish promoter activity by 85%. The factor binding this region is indistinguishable from the cloned nuclear factor NF-Y, as judged from interactions with specific anti-NF-Y monoclonal and polyclonal antibodies. Last, we point out the presence of two sites that share sequence identity to the OAP region of the ARRE-1 site within the IL-2 promoter (K. S. Ullman, W. M. Flanagan, C. A. Edwards, and G. R. Crabtree, Science 254:558-562, 1991). These regions, -85GTGTAATA-78 and -245GTGTAATT-238, reside adjacent to the NF(P) binding sites P1 and P4 and bind a distinct nuclear factor. |
| Databáze: | OpenAIRE |
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