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Argyropoulos, C. et al.

Mining microarray data to identify transcription factors expressed in naÃ¯ve resting but not activated T lymphocytes.

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 naÃ¯ve 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.[1]

References

Mining microarray data to identify transcription factors expressed in naïve resting but not activated T lymphocytes. Argyropoulos, C., Nikiforidis, G.C., Theodoropoulou, M., Adamopoulos, P., Boubali, S., Georgakopoulos, T.N., Paliogianni, F., Papavassiliou, A.G., Mouzaki, A. Genes Immun. (2004) [Pubmed]

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