Regulation of the GATA3 promoter by human T-cell lymphotropic virus type I Tax protein

The HTLV-I nonstructural protein Tax plays a crucial role in cellular transformation. It activates the transcription factors of various cellular genes and interacts with cellular proteins. There is limited data available on the interaction between specific T cell transcription factor GATA3 and Tax. Implications for the significance of GATA3 in T-cell development and function, (Th2) differentiation, and a role of GATA3 during the immune response have been reported. We had previously demonstrated decreased GATA3 mRNA expression in HTLVI infected individuals and in patients with ATLL and HAM/TSP [Gilli et al., 2000]. To determine the effect of the Tax protein on GATA3 gene expression, we investigated the interaction between this protein and its promoter and repressor regions by DNA-protein interaction and “in vitro” transcription assays. Results demonstrated an interaction between Tax and the GATA3 promoter via the transcription factor Sp1 and a role for Tax in the negative regulation of GATA3 expression, through its interaction with the repressor ZEB. This interaction may be involved in the pathophysiology of adult T cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy.