| Autor: |
Argyropoulos, C., Nikiforidis, G.C., Theodoropoulou, M., Adamopoulos, P., Boubali, S., Georgakopoulos, T.N., Paliogianni, F., Papavassiliou, A.G., Mouzaki, A. |
| Předmět: |
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| Zdroj: |
Genes & Immunity; Jan2004, Vol. 5 Issue 1, p16-25, 10p |
| Abstrakt: |
Transcriptional repressors controlling the expression of cytokine genes have been implicated in a variety of physiological and pathological phenomena. An unknown repressor that binds to the distal NFAT element of the interleukin-2 (IL-2) gene promoter in naive T-helper lymphocytes has been implicated in autoimmune phenomena and has emerged as a potentially important factor controlling the latency of HIV-1. The aim of this paper was the identification of this repressor. We resorted to public microarray databases looking for DNA-binding proteins that are present in naïve resting T cells but are downregulated when the cells are activated. A Bayesian data mining statistical analysis uncovered 25 candidate factors. Of the 25, NFAT4 and the oncogene ets-2 bind to the common motif AAGGAG found in the HIV-1 LTR and IL-2 probes. Ets-2 binding site contains the three G's that have been shown to be important for binding of the unknown factor; hence, we considered it the likeliest candidate. Electrophoretic mobility shift assays confirmed cross-reactivity between the unknown repressor and anti-ets-2 antibodies, and cotransfection experiments demonstrated the direct involvement of Ets-2 in silencing the IL-2 promoter. Designing experiments for transcription factor analysis using microarrays and Bayesian statistical methodologies provides a novel way toward elucidation of gene control networks.Genes and Immunity (2004) 5, 16-25. doi:10.1038/sj.gene.6364034 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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